text:
CGP 55398, a liposomal Ge(IV) phthalocyanine bearing two axially ligated cholesterol moieties: a new potential agent for photodynamic therapy of tumours.
Segalla, A.; Milanesi, C.; Jori, G.; Capraro, H. G.; Isele, U.; Schieweck, K.
Ge(IV) phthalocyanine (GePc) with two axially ligated cholesterol moieties was prepared by chemical synthesis and incorporated in a monomeric state into small unilamellar liposomes (CGP 55398). Upon photoexcitation with light wavelengths around its intense absorption peak at 680 nm, GePc shows an efficient photosensitising activity towards biological substrates through a mechanism which largely involves the intermediacy of singlet oxygen. GePc injected systemically into mice bearing an intramuscularly implanted MS-2 fibrosarcoma is quantitatively transferred to serum lipoproteins and localises in the tumour tissue with good efficiency: at 24 h post injection the GePc content in the tumour is 0.74 and 1.87 micrograms per g of tissue with a tumour/peritumoral ratio of 4.35 and 5.67 for injected doses of 0.76 and 1.52 mg kg-1 respectively. At this time the red-light irradiation of the GePc-loaded fibrosarcoma causes a fast and massive tumour necrosis involving both malignant cells and blood vessels. Images Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:8180009
Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine within archaeolipids containing liposomes
Perez, Ana Paula; Casasco, Agustina; Schilrreff, Priscila; Defain Tesoriero, Maria Victoria; Duempelmann, Luc; Altube, Maria Julia; Higa, Leticia; Morilla, Maria Jose; Petray, Patricia; Romero, Eder L
In this work, the in vitro anti-Leishmania activity of photodynamic liposomes made of soybean phosphatidylcholine, sodium cholate, total polar archaeolipids (TPAs) extracted from the hyperhalophile archaea Halorubrum tebenquichense and the photosensitizer zinc phthalocyanine (ZnPcAL) was compared to that of ultradeformable photodynamic liposomes lacking TPAs (ZnPcUDLs). We found that while ZnPcUDLs and ZnPcALs (130 nm mean diameter and ?35 mV zeta potential) were innocuous against promastigotes, a low concentration (0.01 ?M ZnPc and 7.6 ?M phospholipids) of ZnPcALs irradiated at a very low-energy density (0.2 J/cm2) eliminated L. braziliensis amastigotes from J774 macrophages, without reducing the viability of the host cells. In such conditions, ZnPcALs were harmless for J774 macrophages, HaCaT keratinocytes, and bone marrow-derived dendritic cells. Therefore, topical photodynamic treatment would not likely affect skin-associated lymphoid tissue. ZnPcALs were extensively captured by macrophages, but ZnPcUDLs were not, leading to 2.5-fold increased intracellular delivery of ZnPc than with ZnPcUDLs. Despite mediating low levels of reactive oxygen species, the higher delivery of ZnPc and the multiple (caveolin- and clathrin-dependent plus phagocytic) intracellular pathway followed by ZnPc would have been the reason for the higher antiamastigote activity of ZnPcALs. The leishmanicidal activity of photodynamic liposomal ZnPc was improved by TPA-containing liposomes. PMID:25045264
Liposome-bound Zn(II)-phthalocyanine. Mechanisms for cellular uptake and photosensitization
Gry Hege Rodal; Siv Kjersti Rodal; Johan Moan; Kristian Berg
In the present study, cellular uptake of a liposomal formulation of ZnPc(CGP 55847) has been studied in human cervix carcinoma cells of the line NHIK 3025. The cellular uptake of ZnPc is found to be completed after 4–8 h of incubation. The maximum level of ZnPc in the cells after incubation with 1 ?g\\/ml ZnPc in E2a medium containing 3%
Analysis of the photodynamic therapy effects by using chloroaluminum phthalocyanine incorporated into liposomes and fractionation energy in colon tumors of rats
NASA Astrophysics Data System (ADS)
Duarte, Janaina; Hage, Raduan; Tedesco, Antonio C.; Pazos, Marcelo; Martin, Airton A.; Plapler, Helio
Photodynamic therapy (PDT) has been widely studied in the last decades and it is becoming a promising tool in the treatment of tumors of many kinds. PDT is based on photoactivation of a sensitized drug that is restrained in the tumor cells, producing highly reactive species that can destroy tumoral cells with minimum collateral effect. This study aimed to evaluate the effect of the PDT in induced neoplasias of the colon by 1,2-dimetilhidrazine in rats, using as photosensitizing drug the chloroaluminum phthalocyanine incorporated to the liposomes and to compare the methods of irradiation using continuous or fractionated energy in PDT. Ten Wistar rats were distributed randomly in 3 groups (G1, G2 and C), anaesthetized and submitted to PDT with of fractionated (G1) or continuum (G2) irradiation energy using as a source of excitement an InGaAl laser. After 3 hours of the laser irradiation, 2 animals of the G1 group, 2 animals of the G2 group and 1 animal of C group were sacrificed and samples of tumoral tissue were collected for histological analysis; the same procedure was carried through 24 hours after irradiation. There were no significant differences between the extensions of the induced areas of necrosis for PDT in the groups under fractionated or continuous irradiation for the parameters used in this study. New studies must be carried through, using different parameters and intervals of laser irradiation, aiming to maximize the effect of the PDT for the treatment of colon tumors.
Uptake of zinc(II)-phthalocyanine by HepG2 cells expressing the low-density lipoprotein receptor: studies with the liposomal formulation CGP55847
NASA Astrophysics Data System (ADS)
Love, William G.; Havenaar, Ellen C.; Lowe, Philip J.; Taylor, Peter W.
Hydrophobic photosensitizers readily intercalate into plasma lipoproteins. Some tumors acquire cholesterol from the circulation as a result of increased low density lipoprotein (LDL) receptor activity. Thus, circulating LDL may function as a vehicle for the delivery of bound Zn-Pc to cells within a tumor. Zn-Pc:LDL complexes, resulting from the interaction of LDL with the liposomal Zn-Pc formulation CGP55847, bind to the LDL receptor expressed on HepG2 cells but with reduced affinity in comparison to LDL. Confocal fluorescence microscopy facilitated the subcellular localization of Zn-Pc in microcolonies of HepG2 cells; the photosensitizer was distributed throughout the cellular membrane systems but was absent from the cell nucleus. Uptake of Zn-Pc in the presence of LDL was twofold greater than in the absence of the lipoprotein. These data suggest that the LDL uptake pathway may contribute to the localization of Zn-Pc in hyperproliferative tissue.
Comparison of two phthalocyanines for PDT
NASA Astrophysics Data System (ADS)
Bachor, Ruediger; Reich, Ella D.; Graf, Peter; Rueck, Angelika C.; Hautmann, Richard E.
Photodynamic therapy (PDT) is a new treatment modality for bladder carcinoma, especially carcinoma in situ. The goal of our study was to compare two different phthalocyanines for PDT of bladder carcinoma cells and to evaluate phototoxic potential. Material and methods: For PDT hydrophilic chlor-aluminum sulfonated phthalocyanine (CASP) and lipophilic zinc- phthalocyanine (ZnP, CPG 55 847) were compared. For ZnP liposomes as drug carrier were used. The photosensitizer concentrations for both substances used for PDT experiments were 5, 10 and 20 (mu) g/ml. Irradiation was performed with a Penta lamp emitting at wavelengths between 590 and 900 nm at a fluence of up to 12 J/cm2. After irradiation cells were incubated for two days, counted and compared with a control group. Results: The cell survival rate was decreased depending on the light and drug dose. After incubation with the highest drug dose and irradiation with 12 J/cm2 cell survival was 0.03 and 5.5% after incubation with CASP or ZnP, respectively. Light, CASP or ZnP alone had no effect on cells. Studies of the PDT effect by electron microscopy showed intracellular vacuolization caused by mitochondrial damage after incubation with either photosensitizer. Conclusion: The hydrophilic and lipophilic phthalocyanine tested here showed very similar effects on our cell line. ZnP is a pure compound and hence has some advantage over CASP, which is a mixture of a tri- and tetrasulfonated phthalocyanine. In addition, ZnP is administered in liposomes which should enhance tumor selectivity by binding to low density lipoprotein receptors on tumor cells.
Light scattering of human skin: A comparison between zinc(II)— phthalocyanine and photofrin II®
Martin Ochsner
Zinc(II)-phthalocyanine is the active component of the liposomal formulation CGP 55847 which showed a high activity in photodynamic therapy studies on a variety of animal tumours (K. Schieweck et al., SPIE Conf. Proc., 2078 (1994) 107–118).The photophysical properties of zinc(II)-phthalocyanine have been studied in detail and compared with those of Photofrin II®, the only sensitizing agent approved so far for
Sunlight triggered photodynamic ultradeformable liposomes against Leishmania braziliensis are also leishmanicidal in the dark
Jorge Montanari; Cristina Maidana; Mónica Inés Esteva; Cristina Salomon; Maria Jose Morilla; Eder L. Romero
Being independent of artificial power sources, self administered sunlight triggered photodynamic therapy could be a suitable alternative treatment for cutaneous leishmaniasis, that avoids the need for injectables and the toxic side effects of pentavalent antimonials. In this work we have determined the in vitro leishmanicidal activity of sunlight triggered photodynamic ultradeformable liposomes (UDL). ZnPc is a hydrophobic Zn phthalocyanine that
Thermodynamic properties of aqueous Ge(IV) hydroxide complexes from 25 to 350°C: implications for the behavior of germanium and the Ge\\/Si ratio in hydrothermal fluids
Gleb S. Pokrovski; Jacques Schott
The stoichiometry and thermodynamic properties of Ge(IV) hydroxide complexes were generated from both solubility and potentiometric measurements. The solubility of the tetrahedral germanium oxide (GeO2(tetr)) was measured at temperatures from 25 to 350°C in acid to alkaline solutions at the saturated vapor pressure of the system (Psat). Potentiometric measurements were performed on GeO2-KOH aqueous solutions at temperatures from 21 to
Method of solubilizing phthalocyanines and metallophthalocyanines
Rathke, J.W.; Chen, M.J.; Fendrick, C.M.
A one-step method of manufacturing soluble phthalocyanines and metallophthalocyanines, like zinc phthalocyanine, by converting a phthalocyanine or a metallophthalocyanine to a trialkylsilyl-substituted derivative is disclosed. The phthalocyanine or metallophthalocyanine is converted to a soluble trialkylsilyl-substituted derivative by interacting the phthalocyanine or metallophthalocyanine with an active metal amide, like lithium 2,2,6, 6-tetra-methylpiperidide, and a halotrialkylsilane, like chlorotrimethylsilane, to provide a phthalocyanine compound, like phthalocyanine monomers, dimers or polymers, metalated or unmetalated, that are soluble in organic media.
New Directions in Phthalocyanine Pigments
NASA Technical Reports Server (NTRS)
Vandemark, Michael R.
The objectives were the following: (1) investigation of the synthesis of new phthalocyanines; (2) characterization of the new phthalocyanines synthesized; (3) investigate the properties of the newly synthesized phthalocyanines with emphasis on UV protection of plastics and coatings; and (4) utilize quantum mechanics to evaluate the structural relationships with possible properties and synthetic approaches. The proposed research targeted the synthesis of phthalocyanines containing an aromatic bridge between two phthalocyanine rings. The goal was to synthesize pigments which would protect plastics when exposed to the photodegradation effects of the sun in space. The stability and extended conjugation of the phthalocyanines offer a unique opportunity for energy absorption and numerous radiative and non-radiative energy loss mechanisms. Although the original targeted phthalocyanines were changed early in the project, several new and unique phthalocyanine compounds were prepared. The basic goals of this work were met and some unique and unexpected outcomes of the work were the result of the integral use of quantum mechanics and molecular modeling with the synthetic effort.
New directions in phthalocyanine pigments
NASA Technical Reports Server (NTRS)
Trinh, Diep VO
Phthalocyanines have been used as a pigment in coatings and related applications for many years. These pigments are some of the most stable organic pigments known. The phthalo blue and green pigments have been known to be ultraviolet (UV) stable and thermally stable to over 400 C. These phthalocyanines are both a semiconductor and photoconductor, exhibiting catalytic activity and photostabilization capability of polymers. Many metal free and metallic phthalocyanine derivatives have been prepared. Development of the new classes of phthalocyanine pigment could be used as coating on NASA spacecraft material such as glass to decrease the optical degradation from UV light, the outside of the space station modules for UV protection, and coating on solar cells to increase lifetime and efficiency.
Liposome technology. Volume I: Preparation of liposomes
Gregoriadis, G.
These three volumes cover liposome technology in pharmacology and medicine. Contributors emphasize methodology used in their own laboratories, and include a brief introduction, coverage of relevant literature, applications and critical evaluations for the methods they describe. Volume I examine methods for the preparation of liposomes and auxiliary techniques.
Liposomes as nanomedical devices
Bozzuto, Giuseppina; Molinari, Agnese
Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the "first-generation" liposomes, and liposome-based drugs on the market and in clinical trials. PMID:25678787
Copper phthalocyanine and metal free phthalocyanine bulk heterojunction photodetector
NASA Astrophysics Data System (ADS)
Farooq, Amjad; Karimov, Kh. S.; Ahmed, Nisar; Ali, Taimoor; Khalid Alamgir, M.; Usman, Muhammad
In this study we present the dependence of electrical properties of copper phthalocyanine (CuPc) and metal free phthalocyanine (H2Pc) bulk heterojunction structure under different illumination levels. To fabricate the device on ITO coated glass substrate the bulk heterojunction thin film of CuPc and H2Pc with thickness varying from 100 nm to 300 nm are deposited by thermal evaporator. Aluminum thin film was deposited by thermal evaporation as a top contact. The optical properties of the fabricated device are investigated using UV-vis spectroscopy. The current-voltage characteristics in dark and under illumination show that the device is sensitive towards visible light. The absorption spectrum describes its photo sensitivity in the range of wavelength from 200 nm to 850 nm. Simulation of current-intensity of light curve is carried out and experimental results are found in good agreement with simulated ones.
Fused liposome and acid induced method for liposome fusion
Huang, L.; Connor, J.
This patent describes a method of fusing liposomes. It comprises: preparing a suspension of liposomes containing at least one lipid which has a tendency to form the inverted hexagonal phase and at least 20 mol percent of palmitoylhomocysteine; and in the absence of externally added divalent cations, proteins or other macromolecules, acidifying the liposome suspension to reduce the pH of the liposomes to below pH 7, such that at least about 20% of the liposomes fuse to one another.
Frequency domain, time-resolved and spectroscopic investigations of photosensitizers encapsulated in liposomal phantoms
NASA Astrophysics Data System (ADS)
Mermut, Ozzy; Bouchard, Jean-Pierre; Cormier, Jean-Francois; Diamond, Kevin R.; Noiseux, Isabelle; Vernon, Marcia L.; Patterson, Michael S.
A broadband frequency domain fluorescence lifetime system (from ns to ms time scale) has been developed to study the photochemical and photodynamic behavior of model, well-controlled photosensitizer-encapsulating liposomes. Liposomes are known to be efficient and selective photosensitizer (PS) drug delivery vesicles, however, their chemical and physical effects on the photochemical properties of the photosensitizer have not been well characterized. The liposomes employed in this study (both blank and photosensitizer-complexed) were characterized to determine their: a) size distribution (dynamic light scattering), b) image (scanning electron microscope, confocal fluorescence microscopy), c) concentration of particles (flow cytometry), d) temperature-dependant phase transition behavior (differential scanning calorimetry, and e) spectrofluorescent spectrophotometric properties, e.g. aggregation, in the confined environment. The fluorescence decay behavior of two families of encapsulated photosensitizers, di-and tetrasulfonated metallophthalocyanines, and 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH), has been examined as a function of the liposome's physical properties (size-scale, distribution and concentration of scatterer) and the impact of the photosensitizer spatial confinement determined. It is found that the achievable size range and distribution of the PS-liposomes is controlled by the chemical nature of the PS for large liposomes (1000 nm), and is PS independent for small PS-liposomes (~140nm). The lifetime decay behavior was studied for all three photosensitizer-liposome systems and compared before and after confinement. We found the nature of the decay to be similar before and after encapsulation for the sulfonated phthalocyanines containing ionic moieties (primarily monoexponential) but not for HPPH. In the latter, the decay transitioned from multi- to monoexponential decay upon localizing lypophilic HPPH to the liposomal membrane. This behavior was confirmed by obtaining a similar change in lifetime response with an independent timedomain system. We also varied the environment in temperature and oxygen content to examine the effects on the fluorescent lifetimes of the liposomal complexes. The fluorescence decay of all three PS-containing liposomes showed that the local spatial confinement of PS (dictated by the PS chemistry) into different domains within the liposome directly controls the temperature-response. Membrane-bound photosensitizers were less sensitive to temperature effects as illustrated by the decay dynamics observed in solu, that is, they developed a unique decay behavior that correlated with the phase transition of the membrane. The fluorescent lifetime of PS-encapsulated liposomes in deoxygenated environments, relevant to oxygen independent type I phototoxicity, was also probed in the frequency-domain revealing that liposome-confined PS display very different trends than those observed in solu.
Phthalocyanines functionalized with 2-methyl-5-nitro-1H-imidazolylethoxy and 1,4,7-trioxanonyl moieties and the effect of metronidazole substitution on photocytotoxicity.
Wierzchowski, Marcin; Sobotta, Lukasz; Skupin-Mrugalska, Paulina; Kruk, Justyna; Jusiak, Weronika; Yee, Michael; Konopka, Krystyna; Düzgüne?, Nejat; Tykarska, Ewa; Gdaniec, Maria; Mielcarek, Jadwiga; Goslinski, Tomasz
Four novel magnesium(II) and zinc(II) phthalocyanines bearing 1,4,7-trioxanonyl, polyether and/or (2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy, heterocyclic substituents at their non-peripheral positions were synthesized and assessed in terms of physicochemical and biological properties. Magnesium phthalocyanine derivatives bearing polyether substituents (Pc-1), a mixed system of polyether and heterocyclic substituents (Pc-3), and four heterocyclic substituents (Pc-4), respectively, were synthesized following the Linstead macrocyclization reaction procedure. Zinc phthalocyanine (Pc-2) bearing polyether substituents at non-peripheral positions was synthesized following the procedure in n-pentanol with the zinc acetate, and DBU. Novel phthalocyanines were purified by flash column chromatography and characterized using NMR, MS, UV-Vis and HPLC. Moreover, two precursors in macrocyclization reaction phthalonitriles were characterized using X-ray. Photophysical properties of the novel macrocycles were evaluated, including UV-Vis spectra analysis and aggregation study. All macrocycles subjected to singlet oxygen generation and the oxidation rate constant measurements exhibited lower quantum yields of singlet oxygen generation in DMSO than in DMF. In addition, the Pc-2 molecule was found to be the most efficient singlet oxygen generator from the group of macrocycles studied. The photocytotoxicity evaluated on the human oral squamous cell carcinoma cell line, HSC-3, for Pc-3 was significantly higher than that for Pc-1, Pc-2, and Pc-4. Interestingly, Pc-3 was found to be the most active macrocycle in vitro although its ability to generate singlet oxygen was significantly lower than those of Pc-1 and Pc-2. However, attempts to encapsulate phthalocyanines Pc-1-Pc-3 in liposomal membranes were unsuccessful. The phthalocyanine-nitroimidazole conjugate, Pc-4 was encapsulated in phosphatidylglycerol:phosphatidylcholine unilamellar liposomes and subjected to photocytotoxicity study. PMID:23872453
Phthalocyanine blends improve bulk heterojunction solar cells.
Varotto, Alessandro; Nam, Chang-Yong; Radivojevic, Ivana; Tomé, Joao P C; Cavaleiro, José A S; Black, Charles T; Drain, Charles Michael
A core phthalocyanine platform allows engineering of the solubility properties the band gap, shifting the maximum absorption toward the red. A simple method for increasing the efficiency of heterojunction solar cells uses a self-organized blend of phthalocyanine chromophores fabricated by solution processing. PMID:20136126
Optical properties of zinc phthalocyanine nanoparticle dispersions
NASA Astrophysics Data System (ADS)
Nitschke, Christian; O'Flaherty, Seán M.; Kröll, Michael; Doyle, James J.; Blau, Werner J.
We report a study of the fabrication of aqueous nanoparticle dispersions from metallo-phthalocyanine solutions. Furthermore, we examine these nanoparticles using transmission electron and atomic force microscopy (TEM and AFM, respectively). Linear absorption and fluorescence spectroscopy are employed to characterise the novel nanoparticles. Finally, we demonstrate a significant improvement in their nonlinear optical dissipative response compared to dissolved solutions of the same phthalocyanines.
Hexacoordinate bonding and aromaticity in silicon phthalocyanine.
Yang, Yang
Si-E bondings in hexacoordinate silicon phthalocyanine were analyzed using bond order (BO), energy partition, atoms in molecules (AIM), electron localization function (ELF), and localized orbital locator (LOL). Bond models were proposed to explain differences between hexacoordinate and tetracoordinate Si-E bondings. Aromaticity of silicon phthalocyanine was investigated using nucleus-independent chemical shift (NICS), harmonic oscillator model of aromaticity (HOMA), conceptual density functional theory (DFT), ring critical point (RCP) descriptors, and delocalization index (DI). Structure, energy, bonding, and aromaticity of tetracoordinate silicon phthalocyanine were studied and compared with hexacoordinate one. PMID:21105726
incorporation of clodronate-liposomes
Carsten B. SchmidtWeber; Michael Rittig; Eberhard Buchner; Ingeborg Hauser; Frank Emmrich; Raimund W. Kinne
The present study was performed to elu- cidate whether sterically stabilized liposomes laden with clodronate, which lead to depletion of macro- phages (M4s) and amelioration of experimental autoimmune arthritis in vivo, selectively affect cells of the mlineage in vitro. The rates of incorporation of drug-free, fluorescent liposomes and the rates of cell death following exposure to clodronate- liposomes were assessed
Synthesis of Metal Phthalocyanine Sheet Polymers
NASA Technical Reports Server (NTRS)
Achar, B. N.; Fohlen, G. M.; Parker, J. A.
New method for synthesizing metal phthalocyanine tetracarboxylic acids (MPTCA's) yields high purity end product. In addition, high-purity metal phthalocyanine sheet polymers synthesized from compounds. Monomer formed into sheet polymer by heating. Units of polymer linked in manner similar to phenyl-group linkages in biphenyl: Conjugation extends throughout macromolecule, thereby increasing delocalization of TT-electrons. Increases conductivity and thermal stability of polymer.
Journal of Porphyrins and Phthalocyanines J. Porphyrins Phthalocyanines 2011; 15: 301479
Shelnutt, John A.
CONTENTS Journal of Porphyrins and Phthalocyanines J. Porphyrins Phthalocyanines 2011; 15: 301479 pp. 301311 Molecular nanoarchitectures composed of porphyrins and carbon nanomaterials for light and construction of molecular nanoarchitectures of porphyrins and nanoscale carbon materials such as carbon
Journal of Porphyrins and Phthalocyanines J. Porphyrins Phthalocyanines 2011; 15: 115
Shelnutt, John A.
Journal of Porphyrins and Phthalocyanines J. Porphyrins Phthalocyanines 2011; 15: 115 DOI: 10 of synthetic porphyrins in various conformations and envi- ronmentsprovidevaluableinsightsintothemodeofaction of naturally occurring porphyrinic cofactors in proteins. During the last two decades a large body of work has
Journal of Porphyrins and Phthalocyanines J. Porphyrins Phthalocyanines 2011; 15: 727741
Shelnutt, John A.
Journal of Porphyrins and Phthalocyanines J. Porphyrins Phthalocyanines 2011; 15: 727741 DOI: 10 Publishing Company INTRODUCTION The physical properties and chemical reactivities of synthetic porphyrins porphyrinic cofactors in proteins. During the last two decades a large body of work has Steric bulkiness
Superhydrophilic zwitterionic polymers stabilize liposomes.
Cao, Zhiqiang; Zhang, Lei; Jiang, Shaoyi
Nonionic polyethylene glycol (PEG) as a stealth polymer destabilizes liposomes due to its amphiphilic property. As a result, PEGylated liposomes have to be further stabilized, such as by using a large amount cholesterol. This is a long existing dilemma faced by PEG. In this work, we show that zwitterionic poly(carboxybetaine) (PCB) stabilizes liposomes because of its superhydrophilic nature, thus solving this dilemma. Specifically, PCB-modified liposomes without cholesterol exhibited good retention of hydrophilic drug and long blood circulating characteristics in vivo. To further validate this new PCB chemistry, PCB liposomal doxorubicin without cholesterol was compared with DOXIL for their antitumor therapeutic efficacies. PMID:22783927
Waters, Valerie; Ratjen, Felix
Arikace™ is a novel formulation of inhaled liposomal amikacin that can penetrate deep within airway secretions and within Pseudomonas aeruginosa biofilms, making it an attractive therapeutic option for the treatment of cystic fibrosis (CF) pulmonary infections. Initial Phase I and Phase II studies in CF patients with chronic P. aeruginosa infection demonstrated that Arikace™ was a safe drug that resulted in significant improvements in lung function after 14-28 days of treatment. Phase III studies of inhaled liposomal amikacin compared to tobramycin inhalation solution in CF patients with P. aeruginosa infection revealed a comparable increase in forced expiratory volume in 1 second at the end of three cycles. In addition, inhaled liposomal amikacin has other potential applications in the management of difficult-to-treat pulmonary infections. A Phase II trial is currently underway to study the use of Arikace™ for the treatment of recalcitrant nontuberculous mycobacterial lung disease. PMID:24882271
Effect of axial ligation and delivery system on the tumour-localising and -photosensitising properties of Ge(IV)-octabutoxy-phthalocyanines.
Soncin, M.; Polo, L.; Reddi, E.; Jori, G.; Kenney, M. E.; Cheng, G.; Rodgers, M. A.
Four Ge(IV)-octabutoxy-phthalocyanines (GePcs) bearing two alkyl-type axial ligands were assayed for their pharmacokinetic properties and phototherapeutic efficiency in Balb/c mice bearing an intramuscularly transplanted MS-2 fibrosarcoma. The GePcs were i.v. injected at a dose of 0.35 mumol kg-1 body weight after incorporation into either Cremophor emulsions or small unilamellar liposomes of dipalmitoyl-phosphatidylcholine (DPPC). Both the nature of the delivery system and the chemical structure of the phthalocyanine were found to affect the behaviour of the GePcs in vivo. Thus, Cremophor-administered GePcs invariably yielded a more prolonged serum retention and a larger association with low-density lipoproteins (LDLs) as compared with the corresponding liposome-delivered phthalocyanines. This led to a greater efficiency and selectivity of tumour targeting. These effects were more pronounced for those GePcs having relatively long alkyl chains (hexyl to decyl) in the axial ligands. Maximal tumour accumulation (0.67 nmol per g of tissue) was found for Ge-Pc(hexyl)2 at 24 h after injection. Consistently, the Ge-Pc(hexyl)2, administered via Cremophor, showed the highest phototherapeutic activity towards MS-2 fibrosarcoma. PMID:7710936
Studies of phthalocyanine-containing polymers
NASA Astrophysics Data System (ADS)
Lee, Pui Sze Priscilla
This thesis reports the synthesis, spectroscopic and photophysical properties, and in vitro photodynamic activities of several series of phthalocyanine-containing polymers including poly(norbornene), poly(anhydride), and poly(epsilon-caprolactone). Chapter 1 gives a general overview of phthalocyanines including their synthesis and applications. Special emphasis has been placed on hydrophilic and non-aggregated phthalocyanines and their use in photodynamic therapy. In addition, different classes of phthalocyanine-containing polymers will also be mentioned. Chapter 2 discusses the synthesis, characterization, and photophysical properties of a series of poly(norbornene)s with zinc(II) phthalocyanine and amino acid moieties. The copolymers were prepared by copolymerization of 2-(2-norbornenylmethoxy)phthalocyaninatozinc(II) with 5-norbornenes substituted with phenylalanine and tyrosine. As shown by absorption and fluorescence spectroscopy, phthalocyanines in this series of polymer exhibit a rather strong aggregation tendency. Chapter 3 presents the synthesis, characterization, photophysical properties, and in vitro photodynamic activities of a related series of amino acid- and sugar-containing poly(norbornene)s connected axially to a silicon(IV) phthalocyanine core. These polymers exhibit a good solubility in common organic solvents. Due to the axial polymeric substituents, these compounds are free from aggregation and give a high singlet oxygen quantum yield. These polymers in Cremophor EL emulsions also show a high photodynamic activity against HepG2 cells, in particular the polymer with protected galactose moieties. Chapter 4 reports a series of silicon(IV) phthalocyanines substituted with two poly(sebacic anhydride) chains as the axial ligands. The polymers form nanoparticles in water in the presence of surfactants cetyltrimethylammonium bromide (CTAB) and sodium dodecylsulphate (SDS). The degradation of the nanoparticles was carried out in alkaline media and was followed by absorption and fluorescence spectroscopy, and laser light scattering. It was found that phthalocyanines are gradually released during degradation. Chapter 5 describes the preparation, characterization, photophysical properties, and in vitro photodynamic activities of homo- and co-polymers of epsilon-caprolactone and/or 5-ethylene ketyl epsilon-caprolactone connected axially to silicon(IV) phthalocyanine. Again, these polymers are non-aggregated in solution as shown by absorption and fluorescence spectroscopy. Enzymatic degradation of the nanoparticles formed from these polymers with Lipase PS leads to a graduate release of phthalocyanines. In addition, these polymers show high in vitro photodynamic activities toward HepG2 cells, showing that this novel polymer-based colloidal system is potentially useful for the delivery and release of photosensitizers in photodynamic therapy. In addition to polymeric phthalocyanines, a series of symmetrical and unsymmetrical galactose-containing silicon(IV) phthalocyanines has also been prepared. Chapter 6 describes the preparation and properties of these novel compounds, including their in vitro photoactivity toward HepG2 cells. Appendix A gives characterizing data for all the new compounds. Crystallographic details for the X-ray structure determinations are listed in Appendix B.
Boronated liposome development and evaluation
Hawthorne, M.F. [Univ. of California, Los Angeles, CA (United States)
The boronated liposome development and evaluation effort consists of two separate tasks. The first is the development of new boron compounds and the synthesis of known boron species with BNCT potential. These compounds are then encapsulated within liposomes for the second task, biodistribution testing in tumor-bearing mice, which examines the potential for the liposomes and their contents to concentrate boron in cancerous tissues.
Liposomes for Pulmonary Drug Delivery
Janani Swaminathan; Carsten Ehrhardt
\\u000a Liposomes have been widely used in pulmonary drug delivery for multiple applications including solubilization, sustained\\u000a release, cellular and intracellular targeting, minimization of toxicity, and facilitation of absorption. In this chapter,\\u000a formulation aspects, aerosolization, and an extensive overview of the use of pulmonary drug delivery of liposomes for disease\\u000a and drug classes are provided. Specifically, this chapter examines liposomes from in
Ligation strategies for targeting liposomal nanocarriers.
Marqués-Gallego, Patricia; de Kroon, Anton I P M
Liposomes have been exploited for pharmaceutical purposes, including diagnostic imaging and drug and gene delivery. The versatility of liposomes as drug carriers has been demonstrated by a variety of clinically approved formulations. Since liposomes were first reported, research of liposomal formulations has progressed to produce improved delivery systems. One example of this progress is stealth liposomes, so called because they are equipped with a PEGylated coating of the liposome bilayer, leading to prolonged blood circulation and improved biodistribution of the liposomal carrier. A growing research area focuses on the preparation of liposomes with the ability of targeting specific tissues. Several strategies to prepare liposomes with active targeting ligands have been developed over the last decades. Herein, several strategies for the functionalization of liposomes are concisely summarized, with emphasis on recently developed technologies for the covalent conjugation of targeting ligands to liposomes. PMID:25126543
40 CFR 721.9674 - Sulfonated-copper phthalocyanine salt of a triarylmethane dye (generic).
Code of Federal Regulations, 2014 CFR
... 2014-07-01 false Sulfonated-copper phthalocyanine salt of a triarylmethane...Substances § 721.9674 Sulfonated-copper phthalocyanine salt of a triarylmethane...identified generically as sulfonated-copper phthalocyanine salt of a...
40 CFR 721.9674 - Sulfonated-copper phthalocyanine salt of a triarylmethane dye (generic).
Code of Federal Regulations, 2012 CFR
... 2012-07-01 false Sulfonated-copper phthalocyanine salt of a triarylmethane...Substances § 721.9674 Sulfonated-copper phthalocyanine salt of a triarylmethane...identified generically as sulfonated-copper phthalocyanine salt of a...
40 CFR 721.9674 - Sulfonated-copper phthalocyanine salt of a triarylmethane dye (generic).
Code of Federal Regulations, 2010 CFR
... 2010-07-01 false Sulfonated-copper phthalocyanine salt of a triarylmethane...Substances § 721.9674 Sulfonated-copper phthalocyanine salt of a triarylmethane...identified generically as sulfonated-copper phthalocyanine salt of a...
40 CFR 721.9674 - Sulfonated-copper phthalocyanine salt of a triarylmethane dye (generic).
Code of Federal Regulations, 2013 CFR
... 2013-07-01 false Sulfonated-copper phthalocyanine salt of a triarylmethane...Substances § 721.9674 Sulfonated-copper phthalocyanine salt of a triarylmethane...identified generically as sulfonated-copper phthalocyanine salt of a...
40 CFR 721.9674 - Sulfonated-copper phthalocyanine salt of a triarylmethane dye (generic).
Code of Federal Regulations, 2011 CFR
... 2011-07-01 false Sulfonated-copper phthalocyanine salt of a triarylmethane...Substances § 721.9674 Sulfonated-copper phthalocyanine salt of a triarylmethane...identified generically as sulfonated-copper phthalocyanine salt of a...
A Remote Controlled Valve in Liposomes for Triggered Liposomal Release
Arma?an Koçer
In order to reduce the toxicity and increase the efficacy of drugs, there is a need for smart drug delivery systems. Liposomes are one of the promising tools for this purpose. An ideal liposomal delivery system should be stable, long-circulating, accumulate at the target site and release its drug in a controlled manner. Even though there have been many developments
Liposome: classification, preparation, and applications
Liposomes, sphere-shaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid-60s. Today, they are a very useful reproduction, reagent, and tool in various scientific disciplines, including mathematics and theoretical physics, biophysics, chemistry, colloid science, biochemistry, and biology. Since then, liposomes have made their way to the market. Among several talented new drug delivery systems, liposomes characterize an advanced technology to deliver active molecules to the site of action, and at present, several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles to 'second-generation liposomes', in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability and regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents. PMID:23432972
Liposomal Nanomedicines: An Emerging Field
Liposomal nanoparticles (LNs) encapsulating therapeutic agents, or liposomal nanomedicines (LNMs), represent one of the most advanced classes of drug delivery systems, with several currently on the market and many more in clinical trials. During the past 20 years, a variety of tech- niques have been developed for encapsulating both conventional drugs and the new genetic drugs (plasmid DNA-containing therapeutic genes,
Liposome: classification, preparation, and applications
NASA Astrophysics Data System (ADS)
Akbarzadeh, Abolfazl; Rezaei-Sadabady, Rogaie; Davaran, Soodabeh; Joo, Sang Woo; Zarghami, Nosratollah; Hanifehpour, Younes; Samiei, Mohammad; Kouhi, Mohammad; Nejati-Koshki, Kazem
Liposomes, sphere-shaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid-60s. Today, they are a very useful reproduction, reagent, and tool in various scientific disciplines, including mathematics and theoretical physics, biophysics, chemistry, colloid science, biochemistry, and biology. Since then, liposomes have made their way to the market. Among several talented new drug delivery systems, liposomes characterize an advanced technology to deliver active molecules to the site of action, and at present, several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles to `second-generation liposomes', in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability and regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents.
The challenge of liposomes in gene therapy
Francis Martin; Teni Boulikas
Summary Recently, liposomes have gained a special interest as gene delivery systems: over 30 human clinical trials for gene delivery using cationic liposomes have been approved; all these delivery methods use intratumoral, subcutaneous and other local delivery but not systemic delivery due to the toxicity of cationic lipids. Stealth liposomes (coated with polyethyleneglyc ol to camouflage the liposome and evade
Biological activity of liposomal vanillin.
Castan, Leniher; Del Toro, Grisel; Fernández, Adolfo A; González, Manuel; Ortíz, Emilia; Lobo, Daliana
This article presents a study of vanillin encapsulation inside multilamellar liposomes, with emphasis on the evaluation of antioxidant activity, the hemolytic effect, and the antisickling properties of these products. Egg phosphatidylcholine-cholesterol and egg phosphatidylcholine-cholesterol-1-O-decylglycerol liposomes were prepared by mechanical dispersion, all with vanillin included. Vesicles were characterized by determination of encapsulation efficiency and vanillin retention capacity. Antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The hemolytic effect of liposomes was also evaluated by spectrophotometry, as well as the antisickling activity by the Huck test using optical microscopy. Results showed that the lipid composition of liposomes did not significantly affect the encapsulation efficiency. Stable vesicles were obtained with a high retention percentage of vanillin. Liposomes exhibited a high capture of the DPPH radical compared to free vanillin and 1-O-decylglycerol (C10) in solution. Vesicles caused no significant hemolisys in normal erythrocytes, nor in those coming from patients with sickle cell anemia. Vanillin encapsulated in liposomes retained its antisickling activity, with a greater effect for C10-containing vesicles. Our results show that vanillin encapsulation in liposomes is a way to enhance the pharmacologic properties of this molecule using a suitable vehicle. PMID:23767864
Liposome Technology for Industrial Purposes
Wagner, Andreas; Vorauer-Uhl, Karola
Liposomes, spherical vesicles consisting of one or more phospholipid bilayers, were first described in the mid 60s by Bangham and coworkers. Since then, liposomes have made their way to the market. Today, numerous lab scale but only a few large-scale techniques are available. However, a lot of these methods have serious limitations in terms of entrapment of sensitive molecules due to their exposure to mechanical and/or chemical stress. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability. An additional point of view was taken to regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents. PMID:21490754
Crystal fields of porphyrins and phthalocyanines
NASA Astrophysics Data System (ADS)
Johnson, P. S.; Boukahil, I.; Himpsel, F. J.; Kennedy, C.; Jersett, N.; Cook, P. L.; Garcia-Lastra, J. M.
Polarization-dependent X-ray absorption spectroscopy at the N 1s and metal 2p edges is combined with density functional and atomic multiplet calculations to determine the crystal field parameters 10Dq, Ds, and Dt of transition metal (Mn, Fe, Co, Ni) phthalocyanines and octaethylporphyrins. Octaethyl porphyrins are observed to lie flat on Si with native oxide, while phthalocyanines lie on edge. Strong polarization dependence is found at all edges, which facilitates a unique determination of the crystal field parameters. Crystal field values from PBE density functional calculations provide helpful starting values, which are refined by fitting atomic multiplet calculations to the data. Since the crystal field affects electron-hole separation in solar cells, the systematic set of crystal field parameters obtained here can be useful for optimizing dyes for solar cells.
Thermodynamic properties of aqueous Ge(IV) hydroxide complexes from 25 to 350°C: implications for the behavior of germanium and the Ge/Si ratio in hydrothermal fluids
NASA Astrophysics Data System (ADS)
Pokrovski, Gleb S.; Schott, Jacques
The stoichiometry and thermodynamic properties of Ge(IV) hydroxide complexes were generated from both solubility and potentiometric measurements. The solubility of the tetrahedral germanium oxide (GeO 2(tetr)) was measured at temperatures from 25 to 350°C in acid to alkaline solutions at the saturated vapor pressure of the system (P sat). Potentiometric measurements were performed on GeO 2-KOH aqueous solutions at temperatures from 21 to 200°C and P sat using a pH solid-contact glass electrode. Results indicate that Ge(OH) 4°(aq) is the dominant Ge-bearing species at concentrations up to at least 0.05 m over a wide range of pH (0-8) and temperatures (20-350°C). GeO(OH) 3- forms in significant amounts only in alkaline solutions (pH > 8-9). These results were combined with the available low-temperature solubility data on the hexagonal germanium oxide (GeO 2(hex)) and the thermodynamic properties of GeO 2(tetr) and GeO 2(hex) to generate Ge(OH) 4°(aq) and GeO(OH) 3- thermodynamic parameters within the framework of the revised HKF equation of state (Helgeson et al., 1981; Tanger and Helgeson, 1988). Calculations carried out using these parameters indicate that the distribution of Ge hydroxide species as a function of pH and temperature is similar to that of silicon hydroxide complexes. However, the significant differences between Ge(OH) 4°(aq) and Si(OH) 4°(aq) enthalpies of formation and heat capacities can lead to large variations with temperature of Ge/Si ratios in solutions in equilibrium with Ge-bearing silicates. For example, calculations show that the Ge/Si ratio in a fluid in equilibrium with a Ge-bearing wollastonite (Ca(Si,Ge)O 3) increases by an order of magnitude when temperature is raised from 25 to 500°C. This can be responsible for the high values of Ge/Si ratios measured in high temperature crustal fluids.
Scanning tunneling microscopy of metal phthalocyanines
NASA Astrophysics Data System (ADS)
Lu, Xing (Bill)
Scanning tunneling microscopy (STM) images of cobalt(II) phthalocyanine (CoPc), copper(II) phthalocyanine (CuPc), iron(II) phthalocyanine (FePc), and nickel(II) phthalocyanine (NiPc) adsorbed on the Au(111) surface are reported. These species provide images showing sub-molecular structure. A particularly exciting aspect of this work is the strong influence of the metal ion valence configuration on the observed tunneling images. Unlike CuPc and NiPc, wherein the central metal appears as a hole in the molecular image, the cobalt ion in CoPc and iron ion in FePc are the highest points (about 0.25 nm) in the molecular images. These data are interpreted as indicating that the Co(II) dsp7 and Fe(II) dsp6 systems have significant d-orbital character near the Fermi energy while the Cu(II) dsp9 and Ni(II) dsp8 systems do not. This interpretation is consistent with theoretical calculations that predict a large contribution of cobalt and iron d-orbitals near the Fermi energy. An intriguing aspect of this work is that it may be possible to chemically identify different metal complexes simply by their appearance. Metal-organic complex systems of this type may also be viewed as single molecular electronic structures with different parts of the same molecule behaving as insulator, conductor, or semiconductor. A commercial Digital Instruments NanoScope III controller was used with a McAllister Technical UHV STM. Modifications of the preamp, cabling, and coarse approach mechanism were required to achieve satisfactory operation, and these changes are described. Also included are detailed instructions for tip fabrication and final (UHV) electron bombardment cleaning.
Phthalocyanine Tetraamine Epoxy-Curing Agents
NASA Technical Reports Server (NTRS)
Fohlen, G. M.; Achar, B. N.; Parker, J. A.
Tough fire- and chemical-resistant epoxies produced by using metalphthalocyanine tetraamines (MPT's) of copper, cobalt, or nickel as curing agents. Synthesis of MPT's commercially realizable and gives pure compounds with almost 90-percent yield. Synthesis applicable for metals with atomic radii of about 1.35 angstroms, including Cu, Co, Ni, Zn, Fe, Pt, Al, and V. Possible to use metal phthalocyanines to cure epoxy resins in homogeneous reaction.
Phillips, W.T.; Klipper, R.W.; Timmons, J.H.; Rudolph, A.S.
This patent describes a method of preparing stable gamma-emitting radionuclide-labeled alkyleneamine oxime, the incubating being for a period of time sufficient to form labeled liposome-encapsulated protein.
Ciprofloxacin as Ocular Liposomal Hydrogel
Khaled Mohamed Hosny
The purpose of this study was to prepare and characterize an ocular effective prolonged-release liposomal hydrogel formulation\\u000a containing ciprofloxacin. Reverse-phase evaporation was used for preparation of liposomes consisting of soybean phosphatidylcholine\\u000a (PC) and cholesterol (CH). The effect of PC\\/CH molar ratio on the percentage drug encapsulation was investigated. The effect\\u000a of additives such as stearylamine (SA) or dicetyl phosphate (DP)
Pulmonary absorption of liposomal levonorgestrel
Aliasgar Shahiwala; Ambikanandan Misra
The purpose of these studies was to achieve desired bioavailability after pulmonary administration of Levonorgestrel (LN)\\u000a and to provide prolonged effective concentration of the drug in plasma and to reduce reported side effects of orally administered\\u000a drug. The plain drug suspension, physical mixture (plain drug with liposomal constituents), and drug-encapsulated liposomes\\u000a containing 10 ?g of drug were instilled intratracheally in
Phospholipid liposomes functionalized by protein
NASA Astrophysics Data System (ADS)
Glukhova, O. E.; Savostyanov, G. V.; Grishina, O. A.
Finding new ways to deliver neurotrophic drugs to the brain in newborns is one of the contemporary problems of medicine and pharmaceutical industry. Modern researches in this field indicate the promising prospects of supramolecular transport systems for targeted drug delivery to the brain which can overcome the blood-brain barrier (BBB). Thus, the solution of this problem is actual not only for medicine, but also for society as a whole because it determines the health of future generations. Phospholipid liposomes due to combination of lipo- and hydrophilic properties are considered as the main future objects in medicine for drug delivery through the BBB as well as increasing their bioavailability and toxicity. Liposomes functionalized by various proteins were used as transport systems for ease of liposomes use. Designing of modification oligosaccharide of liposomes surface is promising in the last decade because it enables the delivery of liposomes to specific receptor of human cells by selecting ligand and it is widely used in pharmacology for the treatment of several diseases. The purpose of this work is creation of a coarse-grained model of bilayer of phospholipid liposomes, functionalized by specific to the structural elements of the BBB proteins, as well as prediction of the most favorable orientation and position of the molecules in the generated complex by methods of molecular docking for the formation of the structure. Investigation of activity of the ligand molecule to protein receptor of human cells by the methods of molecular dynamics was carried out.
Room temperature ferromagnetism in a phthalocyanine based carbon material
Honda, Z., E-mail: firstname.lastname@example.com; Sato, K.; Sakai, M.; Fukuda, T.; Kamata, N. [Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Hagiwara, M.; Kida, T. [KYOKUGEN (Center for Quantum Science and Technology under Extreme Conditions), Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531 (Japan)
We report on a simple method to fabricate a magnetic carbon material that contains nitrogen-coordinated transition metals and has a large magnetic moment. Highly chlorinated iron phthalocyanine was used as building blocks and potassium as a coupling reagent to uniformly disperse nitrogen-coordinated iron atoms on the phthalocyanine based carbon material. The iron phthalocyanine based carbon material exhibits ferromagnetic properties at room temperature and the ferromagnetic phase transition occurs at T{sub c}?=?490?±?10?K. Transmission electron microscopy observation, X-ray diffraction analysis, and the temperature dependence of magnetization suggest that the phthalocyanine molecules form three-dimensional random networks in the iron phthalocyanine based carbon material.
Encapsulation of small spherical liposome into larger flaccid liposome induced by human plasma proteins
Iglic, Ales
Encapsulation of small spherical liposome into larger flaccid liposome induced by human plasma ) We show that human plasma can induce the encapsulation of small spherical liposomes into larger flaccid liposomes. To explain the observed phenomena, it is proposed that the orientational ordering
Structural Thermodynamics of Cationic Liposome DNA System
Hernández Contreras, Martín
Structural Thermodynamics of Cationic Liposome DNA System O. González-Amezcua and M. Hernández.P. 14-740, México Distrito Federal, Mexico Abstract. Cationic liposomes serve as useful vehicles form two dimen- sional crystalline arrays in the carrier liposome interior. One expects that a precise
How to Stabilize Phospholipid Liposomes (Using Nanoparticles)
Granick, Steve
How to Stabilize Phospholipid Liposomes (Using Nanoparticles) Liangfang Zhang and Steve Granick The simple strategy of mixing phospholipid liposomes with charged nanoparticles and using sonication to mix them at low volume fraction produces particle-stabilized liposomes that repel one another and do
Advantages of liposomal delivery systems for anthracyclines.
Allen, Theresa M; Martin, Francis J
Liposomes, closed vesicular structures consisting of one or more lipid bilayers, have generated a great deal of interest as drug delivery vehicles. In particular, they have been investigated for their ability to improve the delivery of chemotherapeutic agents to tumors, in efforts to increase therapeutic efficacy and decrease toxicity to normal cells. Development of liposomal chemotherapeutic agents has, in the past, been hindered primarily by the rapid uptake of liposomes by the reticuloendothelial system. Numerous strategies that seek to either exploit or avoid this phenomenon have been used. As a result, several liposomal chemotherapeutic agents are now available in the clinic. STEALTH, a novel liposomal system coated with polyethylene glycol, avoids uptake by the reticuloendothelial system, thus improving drug delivery to the tumor while decreasing toxicity. In pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), this delivery system encapsulates doxorubicin within polyethylene glycol-coated liposomes, leading to promising new applications for a well-established drug. Liposome-encapsulated doxorubicin citrate complex (Myocet [NPLD]), another liposomal delivery system for doxorubicin, lacks the polyethylene glycol coating, resulting in much shorter circulation times than those of PLD. Daunorubicin citrate liposome (DaunoXome [DNX]) contains daunorubicin encapsulated in a smaller liposome of a different lipid composition. It has circulation times between those of PLD and NPLD. This article reviews the advantages of liposomal delivery systems in general and the divergent approaches that have been taken in developing these agents. PMID:15717735
Polysaccharide-anchored fatty acid liposome.
Tan, Hsiao Wei; Misran, Misni
In this study, the preparation of N-pamitoyl chitosan (ChP) anchored oleic acid (OA) liposome was demonstrated. Two different types of water-soluble ChPs with different degrees of acylation (DA) were selected for this study. The presence of ChPs on the surface of OA liposome was confirmed with their micrographs and physicochemical properties. The "peeling off" effect on the surface of the ChP-anchored OA (OAChP) liposomes was observed on the atomic force microscope micrographs and confirmed the presence of the ChPs layer on the liposome surface. The surface tension of the OAChPs liposome solution was found to be higher than that of the OA liposome solution. This result indicated the removal of OA monomer by ChPs from the air-water interface. The increase in the minimum area per headgroup (A(min)) of the OA with the presence of ChPs has further proved the interaction between OA monomer and the hydrophobic moieties of the ChPs. The ChPs anchored onto the OA monolayer increased the curvature of the OAChP liposomes monolayer and reduced the liposome size. The size of the OAChP liposomes was reduced by 30 nm as compared with the unmodified OA liposome. Results revealed that the anchored ChPs can improve the integrity and rigidity of the OA liposome. PMID:23174410
The optical functions of metal phthalocyanines
NASA Astrophysics Data System (ADS)
Liu, Z. T.; Kwok, H. S.; Djurisic, A. B.
The optical properties of five metal phthalocyanines (MPcs) thin films (cobalt phthalocyanine (Pc), copper Pc, iron Pc (FePc), nickel Pc, and zinc Pc), were studied by spectroscopic ellipsometry. Thin films of these MPcs were evaporated in high vacuum onto glass substrates, quartz substrates, and silicon substrates. Spectroscopic ellipsometry measurements were performed in the wavelength range 250-800 nm. The absorption spectra were measured, and the film thickness and surface roughness were studied by atomic force microscopy. Determination of optical functions was performed by simultaneous fitting of the experimental data for samples on glass and silicon substrates. Fitting results using point-to-point fitting, the Lorentz model, the modified Lorentz model, the relaxed Lorentz model, and the dual Lorentz model were compared. Models with six oscillators were used to fit the optical functions of FePc, while five oscillators were used for the other four Pcs. It was found that modifications of the Lorentz model are more suitable for description of the optical functions of the MPcs compared with the conventional Lorentz model.
Polymerized liposomes as potential oral vaccine carriers: Stability and bioavailability
Hongming Chen; Vladimir Torchilin; Robert Langer
The potential of polymerized liposomes as oral vaccine carriers is evaluated. The stability of polymerized liposomes is demonstrated in mouse gastrointestinal tracts using dual-labeled liposomes. Similar transit kinetics displayed by the two labels of different hydrophobicity indicate the intactness of the polymerized liposomes inside the gastrointestinal tract. Uptake of liposomes from mouse gastrointestinal tract by Peyer's patches is quantified by
The size of liposomes: a factor which affects their targeting efficiency to tumors and therapeutic activity of liposomal antitumor drugs
A Nagayasu; K Uchiyama; H Kiwada
The size of liposomes has been shown to be an important factor in the efficient delivery of an antitumor agent to a tumor. In this paper, the effects of the size of liposomes on the pharmacokinetics of liposomes and liposome-encapsulated drugs are discussed with reference to: (1) the circulation amount and residence time of liposomes in the blood, (2) the
Structural phase transition in Langmuir films of vanadyl phthalocyanine
NASA Astrophysics Data System (ADS)
Levshin, N. L.; Yudin, S. G.; Krylova, E. A.; Zlatkin, A. T.
The Langmuir-Blodgett films based on vanadyl phthalocyanine (NHSO2C18H37)4 were studied. By the method of piezoresonance quartz balance, the isotherms of adsorption of water, pyridine, and hexane on film surfaces were obtained. A structural phase transition in the Langmuir films of vanadyl phthalocyanine at about 313 K was revealed. The phase transition was observed in ultrathin films and disappeared as the number of layers increased.
Composite LB films of copper octabutoxy phthalocyanine and polyimide
F Jing; R. A Kareem; M. P Srinivasan
Composite LB films of copper octabutoxy phthalocyanine (Cu-obo-Pc) and polyimide from polyamic acid alkyl amine salt have been deposited. The multilayers were formed from mixed Langmuir films and by alternate layer deposition. Analyses were by polarised UV–visible spectroscopy and X-ray diffraction. The phthalocyanine component retained its order in the matrix even after the composite was thermally imidised. The orientations of
Electronic structure and bonding in metal phthalocyanines, Metal=Fe, Co, Ni, Cu, Zn, Mg
NASA Astrophysics Data System (ADS)
Liao, Meng-Sheng; Scheiner, Steve
Electronic structure and bonding in metal phthalocyanines (Metal=Fe, Co, Ni, Cu, Zn, Mg) is investigated in detail using a density functional method. The metal atoms are strongly bound to the phthalocyanine ring in each case, by as much as 10 eV. The calculated orbital energy levels and relative total energies of these D4h structures indicate that Fe and Co phthalocyanines have 3A2g and 2Eg ground states, respectively, but that these states are changed upon interaction with strong-field axial ligands. The valence electronic structures of Fe and Co phthalocyanines differ significantly from those of the others. The HOMOs in Fe, Co, and Cu phthalocyanine are metal 3d-like, whereas in Ni and Zn phthalocyanines, the HOMO is localized on the phthalocyanine ring. The first ionization removes an electron from the phthalocyanine a1u orbital in all cases, with very little sensitivity of the ionization energy to the identity of the metal. Whereas the first reduction in Fe and Co phthalocyanine occurs at the metal, it is the phthalocyanine that is reduced upon addition of an electron to the other systems. Fe, Ni, and Cu phthalocyanines have smaller HOMO-LUMO separations than do Zn and Co phthalocyanine. There is very little variation in atomic charges within the phthalocyanine from one metal to the next.
Capacious and programmable multi-liposomal carriers
NASA Astrophysics Data System (ADS)
Yaroslavov, Alexander A.; Sybachin, Andrey V.; Zaborova, Olga V.; Migulin, Vasiliy A.; Samoshin, Vyacheslav V.; Ballauff, Matthias; Kesselman, Ellina; Schmidt, Judith; Talmon, Yeshayahu; Menger, Fredric M.
Spherical polycationic brushes (SPBs) were synthesized by grafting polycationic chains onto 100 nm polystyrene particles. These particles were exposed to unilamellar egg-lecithin (EL) liposomes with a mean diameter of 40 nm that had been rendered anionic via the presence of 10 molar% of phosphatidylserine (PS1-). The liposomes also contained 30 mole% of a morpholinocyclohexanol-based lipid (MOCH) that undergoes a conformational flip when the pH is decreased from 7.0 to 5.0. Mixtures of SPBs and liposomes at pH 7 gave an electrostatically-driven complex possessing, on average, about 40 liposomes for each SPB particle. It was found that the bound liposomes rapidly release much of their contents when the pH is reduced from 7.0 to 5.0 owing mostly to a MOCH conformational change that creates defects in the bilayer membrane. The drop in pH does not, however, induce a separation of the liposomes from the SPBs. Around 50-60% of the liposome contents escape before, it is reasoned, lateral and transmembrane motion of the membrane components heals the defects and prevents further release. Remarkably, the liposomes complexed with SPB release their cargo much faster than the identical but non-complexed liposomes.Spherical polycationic brushes (SPBs) were synthesized by grafting polycationic chains onto 100 nm polystyrene particles. These particles were exposed to unilamellar egg-lecithin (EL) liposomes with a mean diameter of 40 nm that had been rendered anionic via the presence of 10 molar% of phosphatidylserine (PS1-). The liposomes also contained 30 mole% of a morpholinocyclohexanol-based lipid (MOCH) that undergoes a conformational flip when the pH is decreased from 7.0 to 5.0. Mixtures of SPBs and liposomes at pH 7 gave an electrostatically-driven complex possessing, on average, about 40 liposomes for each SPB particle. It was found that the bound liposomes rapidly release much of their contents when the pH is reduced from 7.0 to 5.0 owing mostly to a MOCH conformational change that creates defects in the bilayer membrane. The drop in pH does not, however, induce a separation of the liposomes from the SPBs. Around 50-60% of the liposome contents escape before, it is reasoned, lateral and transmembrane motion of the membrane components heals the defects and prevents further release. Remarkably, the liposomes complexed with SPB release their cargo much faster than the identical but non-complexed liposomes. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06037g
Topology of Multivesicular Liposomes, a Model Biliquid Foam
Zasadzinski, Joseph A.
Topology of Multivesicular Liposomes, a Model Biliquid Foam M. S. Spector and J. A. Zasadzinski was used to characterize the microstructure of a novel multivesicular liposome (MVL) currently under drugs in conventional liposomes allows forlong-termreleaseofdrugsattherapeuticdosages,while avoiding
Preparation, Biodistribution and Neurotoxicity of Liposomal Cisplatin following Convection Enhanced
Paris-Sud XI, Université de
Preparation, Biodistribution and Neurotoxicity of Liposomal Cisplatin following Convection Enhanced was to evaluate two novel liposomal formulations of cisplatin as potential therapeutic agents for treatment described in detail by other investigators. The CHEMS liposomal formulation had a Pt loading efficiency
Photophysical studies of newly derivatized mono substituted phthalocyanines grafted onto silica nanoparticles via click chemistry.
Fashina, Adedayo; Amuhaya, Edith; Nyokong, Tebello
This work reports on the synthesis, characterization and photophysical studies of newly derived phthalocyanine complexes and the phthalocyanine-silica nanoparticles conjugates. The derived phthalocyanine complexes have one terminal alkyne group. The derived phthalocyanine complexes showed improved photophysical properties (?F, ?T, ?? and ?T) compared to the respective phthalocyanine complexes from which they were derived. The derived phthalocyanine complexes were conjugated to the surface of an azide functionalized silica nanoparticles via copper (1) catalyzed cyclo-addition reaction. All the conjugates showed lower triplet quantum yields ranging from 0.37 to 0.44 compared to the free phthalocyanine complexes. The triplet lifetimes ranged from 352 to 484 ?s for the conjugates and from 341 to 366 ?s for the free phthalocyanine complexes. PMID:25615674
Lung specific stealth liposomes: stability, biodistribution and toxicity of liposomal antitubercular drugs in mice
Parampal Deol; G. K Khuller
Liposomes with enhanced affinity towards lung tissue were prepared for the development of more effective chemotherapy against tuberculosis. Modification of surface of stealth liposomes by tagging O-stearylamylopectin (O-SAP) resulted in the increased affinity of these liposomes towards lung tissue of mice. Liposomes containing egg phosphatidylcholine (ePC), cholesterol (CH), dicetylphosphate (DCP), O-SAP and monosialogangliosides (GM1)\\/distearylphosphatidylethanolamine-poly(ethylene glycol) 2000 (DSPE-PEG 2000) were found
Phthalocyanine nanoparticle formation in supersaturated solutions.
Van Keuren, Edward; Bone, Alysia; Ma, Changbao
Self-organization of molecules in solution is an important natural and synthetic process, in particular for the preparation of nanomaterials. However, the mechanism of growth for solution-based nanoparticle formation is not always well understood. We present results that clarify these mechanisms in solutions of magnesium phthalocyanine in which the self-organization is induced by addition of a miscible nonsolvent. From simultaneous measurements of the sizes of the growing nanoparticles by photon correlation spectroscopy and the molecular concentration by absorption and fluorescence spectroscopy, we have found that the particles do not grow by molecular diffusion to the surfaces. These results suggest the importance of unstable clusters in the growth process. We also observed a strong dependence of the particle size on the initial concentration which we attribute to effects of the curvature of the solubility curve. PMID:18479155
Bupivacaine Liposomal Versus Bupivacaine: Comparative Review
Pierce, Deirdre P.; Whalen, Karen; Guharoy, Roy; Hildreth, Kenneth
Abstract Bupivacaine liposomal injection was recently approved by the US Food and Drug Administration (FDA) as a local anesthetic for use in management of postsurgical pain in adults. When compared to placebo, bupivacaine liposomal decreases postoperative pain and opioid use. This review examines the efficacy of bupivacaine liposomal when compared to conventional bupivacaine ± epinephrine using published and unpublished data provided to the FDA by the manufacturer. PMID:24958971
Continuous wasteless ecologically safe technology of propylenecarbonate production in presence of phthalocyanine catalysts
Afanasiev, Vladimir Vasilievich (Moscow, RU); Zefirov, Nikolai Serafimovich (Moscow, RU); Zalepugin, Dmitry Yurievich (Moscow, RU); Polyakov, Victor Stanislavovich (Moscow, RU); Tilkunova,Nataliya Alexandrovna (Moscow, RU); Tomilova, Larisa Godvigovna (Moscow, RU)
A continuous method of producing propylenecarbonate includes carboxylation of propylene oxide with carbon dioxide in presence of phthalocyanine catalyst on an inert carrier, using as the phthalocyanine catalyst at least one catalyst selected from the group consisting of not-substituted, methyl, ethyl, butyl, and tret butyl-substituted phthalocyanines of metals, including those containing counterions, and using as the carrier a hydrophobic carrier.
Pegylated liposomal doxorubicin in ovarian cancer
Green, Andrew E; Rose, Peter G
Pegylated liposomal doxorubicin is a formulation of doxorubicin in which the molecule itself is packaged in a liposome made of various lipids with an outer coating of polyethylene glycol. Liposomal technology is being used in increasing amounts in the therapy of a variety of cancers, including ovarian cancers. This article reviews the mechanistic actions of this formulation, the Phase II and Phase III data that helped define the role of pegylated liposomal doxorubicin in recurrent ovarian cancer, as well as a discussion of some of the side-effects and their management. PMID:17717964
Tumor targeting using liposomal antineoplastic drugs
Huwyler, Jörg; Drewe, Jürgen; Krähenbühl, Stephan
During the last years, liposomes (microparticulate phospholipid vesicles) have been used with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumor drugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vector-conjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this field of research. PMID:18488413
Capacious and programmable multi-liposomal carriers.
Yaroslavov, Alexander A; Sybachin, Andrey V; Zaborova, Olga V; Migulin, Vasiliy A; Samoshin, Vyacheslav V; Ballauff, Matthias; Kesselman, Ellina; Schmidt, Judith; Talmon, Yeshayahu; Menger, Fredric M
Spherical polycationic brushes (SPBs) were synthesized by grafting polycationic chains onto 100 nm polystyrene particles. These particles were exposed to unilamellar egg-lecithin (EL) liposomes with a mean diameter of 40 nm that had been rendered anionic via the presence of 10 molar% of phosphatidylserine (PS(1-)). The liposomes also contained 30 mole% of a morpholinocyclohexanol-based lipid (MOCH) that undergoes a conformational flip when the pH is decreased from 7.0 to 5.0. Mixtures of SPBs and liposomes at pH 7 gave an electrostatically-driven complex possessing, on average, about 40 liposomes for each SPB particle. It was found that the bound liposomes rapidly release much of their contents when the pH is reduced from 7.0 to 5.0 owing mostly to a MOCH conformational change that creates defects in the bilayer membrane. The drop in pH does not, however, induce a separation of the liposomes from the SPBs. Around 50-60% of the liposome contents escape before, it is reasoned, lateral and transmembrane motion of the membrane components heals the defects and prevents further release. Remarkably, the liposomes complexed with SPB release their cargo much faster than the identical but non-complexed liposomes. PMID:25554444
Sunlight triggered photodynamic ultradeformable liposomes against Leishmania braziliensis are also leishmanicidal in the dark.
Montanari, Jorge; Maidana, Cristina; Esteva, Mónica Inés; Salomon, Cristina; Morilla, Maria Jose; Romero, Eder L
Being independent of artificial power sources, self administered sunlight triggered photodynamic therapy could be a suitable alternative treatment for cutaneous leishmaniasis, that avoids the need for injectables and the toxic side effects of pentavalent antimonials. In this work we have determined the in vitro leishmanicidal activity of sunlight triggered photodynamic ultradeformable liposomes (UDL). ZnPc is a hydrophobic Zn phthalocyanine that showed 20% anti-promastigote activity (APA) and 20% anti-amastigote activity (AA) against Leishmania braziliensis (strain 2903) after 15min sunlight irradiation (15J/cm(2)). However, when loaded in UDL as UDL-ZnPc (1.25?M ZnPc-1mM phospholipids) it elicited 100% APA and 80% AA at the same light dose. In the absence of host cell toxicity, UDL and UDL-ZnPc also showed non-photodynamic leishmanicidal activity. Confocal laser scanning microscopy of cryosectioned human skin mounted in non-occlusive Saarbrücken Penetration Model, showed that upon transcutaneous administration ZnPc penetrated nearly 10 folds deeper as UDL-ZnPc than if loaded in conventional liposomes (L-ZnPc). Quantitative determination of ZnPc confirmed that UDL-ZnPc penetrated homogeneously in the stratum corneum, carrying 7 folds higher amount of ZnPc 8 folds deeper than L-ZnPc. It is envisioned that the multiple leishmanicidal effects of UDL-ZnPc could play a synergistic role in prophylaxis or therapeutic at early stages of the infection. PMID:20727925
Liposome adhesion generates traction stress
NASA Astrophysics Data System (ADS)
Murrell, Michael P.; Voituriez, Raphaël; Joanny, Jean-François; Nassoy, Pierre; Sykes, Cécile; Gardel, Margaret L.
Mechanical forces generated by cells modulate global shape changes required for essential life processes, such as polarization, division and spreading. Although the contribution of the cytoskeleton to cellular force generation is widely recognized, the role of the membrane is considered to be restricted to passively transmitting forces. Therefore, the mechanisms by which the membrane can directly contribute to cell tension are overlooked and poorly understood. To address this, we directly measure the stresses generated during liposome adhesion. We find that liposome spreading generates large traction stresses on compliant substrates. These stresses can be understood as the equilibration of internal, hydrostatic pressures generated by the enhanced membrane tension built up during adhesion. These results underscore the role of membranes in the generation of mechanical stresses on cellular length scales and that the modulation of hydrostatic pressure due to membrane tension and adhesion can be channelled to perform mechanical work on the environment.
Sirolimus encapsulated liposomes for cancer therapy: physicochemical and mechanical characterization of sirolimus distribution within liposome bilayers.
Onyesom, Ichioma; Lamprou, Dimitrios A; Sygellou, Lamprini; Owusu-Ware, Samuel K; Antonijevic, Milan; Chowdhry, Babur Z; Douroumis, Dennis
Sirolimus has recently been introduced as a therapeutic agent for breast and prostate cancer. In the current study, conventional and Stealth liposomes were used as carriers for the encapsulation of sirolimus. The physicochemical characteristics of the sirolimus liposome nanoparticles were investigated including the particle size, zeta potential, stability and membrane integrity. In addition atomic force microscopy was used to study the morphology, surface roughness and mechanical properties such as elastic modulus deformation and deformation. Sirolimus encapsulation in Stealth liposomes showed a high degree of deformation and lower packing density especially for dipalmitoyl-phosphatidylcholine (DPPC) Stealth liposomes compared to unloaded. Similar results were obtained by differential scanning calorimetry (DSC) studies; sirolimus loaded liposomes were found to result in a distorted state of the bilayer. X-ray photon electron (XPS) analysis revealed a uniform distribution of sirolimus in multilamellar DPPC Stealth liposomes compared to a nonuniform, greater outer layer lamellar distribution in distearoylphosphatidylcholine (DSPC) Stealth liposomes. PMID:24099044
Methods for using redox liposome biosensors
Cheng, Quan (SF, CA); Stevens, Raymond C. (La Jolla, CA)
The present invention provides methods and compositions for detecting the presence of biologically-important analytes by using redox liposome biosensors. In particular, the present invention provides liposome/sol-gel electrodes suitable for the detection of a wide variety of organic molecules, including but not limited to bacterial toxins.
Structure of DNA-liposome complexes
Lasic, D.D. [MegaBios Corporation, Burlingame, CA (United States)] [MegaBios Corporation, Burlingame, CA (United States); Strey, H.; Podgornik, R. [National Inst. of Health, Bethesda, MD (United States)] [National Inst. of Health, Bethesda, MD (United States); Stuart, M.C.A.; Frederik, P.M. [Limburg Univ., Maastricht (Netherlands)] [Limburg Univ., Maastricht (Netherlands)
Despite numerous studies and commericially available liposome kits, however, the structure of DNA-cationic liposome complexes is still not yet well understood. We have investigated the structure of these complexes using high-resolution cryo electron microscopy (EM) and small angle X-ray scattering (SAXS). 14 refs., 3 figs.
Liposomal Nanocapsules in Food Science and Agriculture
T. Matthew Taylor; Jochen Weiss; P. Michael Davidson; Barry D. Bruce
Liposomes, spherical bilayer vesicles from dispersion of polar lipids in aqueous solvents, have been widely studied for their ability to act as drug delivery vehicles by shielding reactive or sensitive compounds prior to release. Liposome entrapment has been shown to stabilize encapsulated, bioactive materials against a range of environmental and chemical changes, including enzymatic and chemical modification, as well as
Synthesis and photodynamic activity of novel asymmetrically substituted fluorinated phthalocyanines.
Sharman, Wesley M; van Lier, Johan E
A series of asymmetrically substituted dodecafluorinated phthalocyanines has been synthesized via the Kobayashi ring expansion reaction of the corresponding dodecafluorinated boron subphthalocyanine with differently substituted 1,3-diiminoisoindolines. The mild reaction conditions employed during this ring expansion reaction gave rise exclusively to 3:1 asymmetrically substituted dodecafluorinated phthalocyanines. Metal insertion into the metal-free phthalocyanines was accomplished by heating at 40 degrees C in N,N-dimethylformamide in the presence of zinc bromide. The resulting zinc dodecafluorophthalocyanines were formulated as Cremophor EL oil-water emulsions and evaluated as photosensitizers in vitro against EMT-6 mouse mammary tumor cells. As compared to the previously studied zinc hexadecafluorophthalocyanine, these new asymmetrical zinc dodecafluorophthalocyanines exhibited improved photodynamic activity. PMID:16173794
Complementary Liposomes Based on Phosphatidylcholine: Interaction Effectiveness vs Protective Coating
Alexandros Pantos; Zili Sideratou; Constantinos M. Paleos
A prospective targeted drug delivery system was prepared by the introduction of complementary and protective moieties at the external surfaces of liposomes. Thus recognition between hydrogenated phosphatidylcholine–cholesterol-based liposomes was achieved by the interaction of the complementary phosphate and guanidinium groups incorporated in separate liposomes while polyethylene glycol chains (PEG) protected both liposomes from environmental factors. In general, protective coating of
Fusigenic Viral Liposome for Gene Therapy in Cardiovascular Diseases
Victor J. Dzau; Michael J. Mann; Ryuichi Morishita; Yasufumi Kaneda
To improve the efficiency of liposome-mediated DNA transfer as a tool for gene therapy, we have developed a fusigenic liposome vector based on principles of viral cell fusion. The fusion proteins of hemagglutinating virus of Japan (HVJ; also Sendai virus) are complexed with liposomes that encapsulate oligodeoxynucleotide or plasmid DNA. Subsequent fusion of HVJ-liposomes with plasma membranes introduces the DNA
Neuronal chemotaxis by optically manipulated liposomes
NASA Astrophysics Data System (ADS)
Pinato, G.; Lien, L. T.; D'Este, E.; Torre, V.; Cojoc, D.
We probe chemotaxis of single neurons, induced by signalling molecules which were optically delivered from liposomes in the neighbourhood of the cells. We implemented an optical tweezers setup combined with a micro-dissection system on an inverted microscope platform. Molecules of Netrin-1 protein were encapsulated into micron-sized liposomes and manipulated to micrometric distances from a specific growth cone of a hippocampal neuron by the IR optical tweezers. The molecules were then released by breaking the liposomes with UV laser pulses. Chemotaxis induced by the delivered molecules was confirmed by the migration of the growth cone toward the liposome position. Since the delivery can be manipulated with high temporal and spatial resolution and the number of molecules released can be controlled quite precisely by tuning the liposome size and the solution concentration, this technique opens new opportunities to investigate the effect of physiological active compounds as Netrin-1 to neuronal signalling and guidance, which represents an important issue in neurobiology.
Ketoprofen-liposomes formulation for clinical therapy.
Tar??u, Liliana; Cazacu, Ana; Melnig, V
Lipid (L-?-phosphatidylcholine) was used in liposome-ketoprofen formulation to obtain vesicles systems characterized by a net positive charge along the liposomal surface. A careful analysis of vesicles formation and systems stability was made. Dynamic stability and specificity of liposomes disruption and prolonged release of ketoprofen was provided by steric effect accomplished on the vesicle surface by chitosan molecules, which were introduced into the system additionally. The retardation effect of the liposomes containing ketoprofen was tested in vitro and in vivo. The studies have shown that the liposomes containing ketoprofen obtained are characterized by a net positive charge and an average diameter of 1,287 nm for dialyzed solutions (pH 7.40). This formulation presents in vivo significant antinociceptive effects starting at 90 min, with a maximum intensity between 2 and 8 h, prolonged more than 10 h, and an analgesic activity within 3-4 h. PMID:22760402
Phthalocyanine-assisted photodynamic inactivation of pathogenic microorganisms
NASA Astrophysics Data System (ADS)
Mantareva, Vanya; Angelov, Ivan; Borissova, Ekaterina; Avramov, Latchezar; Kussovski, Vesselin
The phthalocyanine zinc(II) and aluminum (III) complexes were studied to photoinactivate the bacterial strains, Staphylococcus aureus, methacillin-sensitive and methacillin-resistant, Pseudomonas aeruginosa and one yeast Candida albicans. The binding of phthalocyanines to bacteria and fungi cells was evaluated by the means of laserinduced fluorescence technique. The fluorescent spectra of dyes (650 - 800 nm) after direct excitation (635 nm) were measured as follows: 1. for the aqua supernatants obtained after 10 min cell incubation with the respected phthalocyanines (1.6 ?mol.l -1), 2. for the washed from the unbound dye cells, and 3. for the organic extracts from the three times washed cells. Fluorescent intensities at the emission maximum (~690 nm) were compared to the spectra of the phthalocyanines in organic solutions. The phthalocyanines uptake data for bacteria and fungi were determined at different cell densities. Nevertheless the better fluorescence properties of AlPc (fluorescent quantum yield of 0.4 towards 0.3 for ZnPcs) the lower drug accumulation in microorganisms was obtained. PDI results indicated an intensive lowering of the bacterial survival of both strains of S. aureus treated with cationic ZnPcMe followed by the anionic ZnPcS, at irradiance of 100 mW cm -2 and fluence rate of 60 J cm -2. More resistant to phototreatment P. aeruginosa and morphologically complicated yeast C. albicans were successfully inactivated only with cationic ZnPcMe. These data indicate the promising future application of cationic phthalocyanine in photodynamic inactivation of pathogenic microorganisms.
Pharmacokinetics of temoporfin-loaded liposome formulations: correlation of liposome and temoporfin blood concentration.
Decker, Christiane; Schubert, Harald; May, Sylvio; Fahr, Alfred
Liposomal formulations of the highly hydrophobic photosensitizer temoporfin were developed in order to overcome solubility-related problems associated with the current therapy scheme. We have incorporated temoporfin into liposomes of varying membrane composition, cholesterol content, and vesicle size. Specifically, two phosphatidyl oligoglycerols were compared to PEG2000-DSPE with respect to the ability to prolong circulation half life of the liposomal carrier. We measured the resulting pharmacokinetic profile of the liposomal carrier and the incorporated temoporfin in a rat model employing a radioactive lipid label and (14)C-temoporfin. The data for the removal of liposomes and temoporfin were analyzed in terms of classical pharmacokinetic theory assuming a two-compartment model. This model, however, does not allow in a straightforward manner to distinguish between temoporfin eliminated together with the liposomal carrier and temoporfin that is first transferred to other blood components (e. g. plasma proteins) before being eliminated from the blood. We therefore additionally analyzed the data based on two separate one-compartment models for the liposomes and temoporfin. The model yields the ratio of the rate constant of temoporfin elimination together with the liposomal carrier and the rate constant of temoporfin elimination following the transfer to e. g. plasma proteins. Our analysis using this model demonstrates that a fraction of temoporfin is released from the liposomes prior to being eliminated from the blood. In case of unmodified liposomes this temoporfin release was observed to increase with decreasing bilayer fluidity, indicating an accelerated temoporfin transfer from gel-phase liposomes to e. g. plasma proteins. Interestingly, liposomes carrying either one of the three investigated surface-modifying agents did not adhere to the tendencies observed for unmodified liposomes. Although surface-modified liposomes exhibited improved pharmacokinetic properties with regard to the liposomal carrier, an enhanced temoporfin loss and elimination from the PEGylated-liposomes was observed. This effect was more pronounced for PEGylated liposomes than for the two oligo-glycerols. Our combined experimental-theoretical approach for in vivo plasma re-distribution of liposomal drugs may help to optimize colloidal drug carrier systems. PMID:23313962
Controllable fabrication of copper phthalocyanine nanostructure crystals.
Liu, Fangmei; Sun, Jia; Xiao, Si; Huang, Wenglong; Tao, Shaohua; Zhang, Yi; Gao, Yongli; Yang, Junliang
Copper phthalocyanine (CuPc) nanostructure crystals, including nanoflower, nanoribbon, and nanowire, were controllably fabricated by temperature gradient physical vapor deposition (TG-PVD) through controlling the growth parameters. In a controllable growth system with carrier gas N2, nanoflower, nanoribbon, and nanowire crystals were formed in a high-temperature zone, medium-temperature zone, and low-temperature zone, respectively. They were proved to be ?-phase, coexist of ?-phase and ?-phase, and ?-phase respectively based on x-ray diffraction results. Furthermore, ultralong CuPc nanowires up to several millimeters could be fabricated by TG-PVD without carrier gas, and they were well-aligned to form large-area CuPc nanowire crystal arrays by the Langmuir-Blodgett method. The nanostructure crystals showed unusual optical absorption spectra from the ultraviolet-visible to near-infrared range, which was explained by the diffraction and scattering caused by the wavelength-sized nanostructures. These CuPc nanostructure crystals show potential applications in organic electronic and optoelectronic devices. PMID:25961155
Controllable fabrication of copper phthalocyanine nanostructure crystals
NASA Astrophysics Data System (ADS)
Liu, Fangmei; Sun, Jia; Xiao, Si; Huang, Wenglong; Tao, Shaohua; Zhang, Yi; Gao, Yongli; Yang, Junliang
Copper phthalocyanine (CuPc) nanostructure crystals, including nanoflower, nanoribbon, and nanowire, were controllably fabricated by temperature gradient physical vapor deposition (TG-PVD) through controlling the growth parameters. In a controllable growth system with carrier gas N2, nanoflower, nanoribbon, and nanowire crystals were formed in a high-temperature zone, medium-temperature zone, and low-temperature zone, respectively. They were proved to be ?-phase, coexist of ?-phase and ?-phase, and ?-phase respectively based on x-ray diffraction results. Furthermore, ultralong CuPc nanowires up to several millimeters could be fabricated by TG-PVD without carrier gas, and they were well-aligned to form large-area CuPc nanowire crystal arrays by the Langmuir–Blodgett method. The nanostructure crystals showed unusual optical absorption spectra from the ultraviolet–visible to near-infrared range, which was explained by the diffraction and scattering caused by the wavelength-sized nanostructures. These CuPc nanostructure crystals show potential applications in organic electronic and optoelectronic devices.
Filamentary resistance switching in phthalocyanine thin films observed by electroluminescence
NASA Astrophysics Data System (ADS)
Meng, Qingyu; He, Xiaochuan; Mao, Qi; Weng, Yuxiang; Yang, Jianbing; Yan, Donghang; Zhao, Hongwu
Metal phthalocyanine heterojunctions with highly stable resistance switching characteristics have been prepared and the switching mechanism has been further investigated by electroluminescence (EL). The point-like EL emission has been observed during switching, demonstrating that the filamentary conduction gives rise to resistance switching. Furthermore, the high correlativity between EL emission sites and domain boundaries of phthalocyanine films has been established, which indicates that the switching process is favorable to occur within the disordered region of organic films. A band-based model has been proposed to describe the EL associated electrical switching mechanism.
Spectroscopic studies on Si-phthalocyanines and Si-naphthalocyanines
NASA Astrophysics Data System (ADS)
von Schoenermark, C.; Volkmer, Andreas; Mueller, Silke; Woehrle, Dieter; Roeder, Beate
Some photophysical properties (steady-state absorption, fluorescence and phosphorescence, fluorescence decay times and singlet oxygen quantum yields) of silicon phthalocyanines with methoxypolyethylene glycol (MPEG)-substituents of various chain length at the silicon atom [SiPc(OCH2CH2)n-OCH3; n equals 1,2,3,12], silicon phthalocyanine covalently bound to the water soluble polymer methoxypolyethylene glycol [SiPc(-O-MPEG 5000)2] and silicon naphthalocyanine [SiNc(CH2CH2OCH3)2] have been studied. The aim of these investigations was to get information about the influence of methoxypolyethylene-glycol-coupling on photophysical sensitizer parameters.
Pancreatic toxicity after liposomal amphotericin B.
Stuecklin-Utsch, A; Hasan, C; Bode, U; Fleischhack, G
Though liposomal amphotericin B has been available in Germany since 1992, efficacy and safety of this formulation of amphotericin B are still not well-documented in children. As far as gastrointestinal side-effects are concerned, an elevated alkaline phosphatase and elevated transaminases have been reported. In our department, liposomal amphotericin B had been used since 1994 to treat patients with proven or suspected fungal infections in a daily dose of 1-3 mg kg-1. Additionally, patients with high-dose chemotherapy and autologous stem cell support received liposomal amphotericin B prophylactically in a dose of 1 mg kg(-1) three times per week. We performed a retrospective analysis of all 31 patients who had received liposomal amphotericin B by 1999. In five patients, an isolated transient elevation of the serum lipase level during, or shortly after, the therapy with liposomal amphotericin B was detected. Three of these patients showed clinical signs of pancreatitis, with one patient displaying slightly elevated transaminases. So far, elevated levels of serum lipase have not been described as a possible side-effect of a liposomal amphotericin B therapy. The pathogenesis of this elevation is unclear. As possible reasons, an enzyme induction due to fat overload or a toxic damage of the pancreatic tissue by the liposomes or amphotericin B itself are discussed. PMID:12100534
Silicon Phthalocyanine 4 Phototoxicity in Trichophyton rubrum
Lam, Minh; Dimaano, Matthew L.; Oyetakin-White, Patricia; Retuerto, Mauricio A.; Chandra, Jyotsna; Mukherjee, Pranab K.; Ghannoum, Mahmoud A.; Cooper, Kevin D.
Trichophyton rubrum is the leading pathogen that causes long-lasting skin and nail dermatophyte infections. Currently, topical treatment consists of terbinafine for the skin and ciclopirox for the nails, whereas systemic agents, such as oral terbinafine and itraconazole, are also prescribed. These systemic drugs have severe side effects, including liver toxicity. Topical therapies, however, are sometimes ineffective. This led us to investigate alternative treatment options, such as photodynamic therapy (PDT). Although PDT is traditionally recognized as a therapeutic option for treating a wide range of medical conditions, including age-related macular degeneration and malignant cancers, its antimicrobial properties have also received considerable attention. However, the mechanism(s) underlying the susceptibility of dermatophytic fungi to PDT is relatively unknown. As a noninvasive treatment, PDT uses a photosensitizing drug and light, which, in the presence of oxygen, results in cellular destruction. In this study, we investigated the mechanism of cytotoxicity of PDT in vitro using the silicon phthalocyanine (Pc) 4 [SiPc(OSi(CH3)2(CH2)3N(CH3)2)(OH)] in T. rubrum. Confocal microscopy revealed that Pc 4 binds to cytoplasmic organelles, and upon irradiation, reactive oxygen species (ROS) are generated. The impairment of fungal metabolic activities as measured by an XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay indicated that 1.0 ?M Pc 4 followed by 670 to 675 nm light at 2.0 J/cm2 reduced the overall cell survival rate, which was substantiated by a dry weight assay. In addition, we found that this therapeutic approach is effective against terbinafine-sensitive (24602) and terbinafine-resistant (MRL666) strains. These data suggest that Pc 4-PDT may have utility as a treatment for dermatophytosis. PMID:24614382
Current status of liposomal porphyrinoid photosensitizers.
Skupin-Mrugalska, Paulina; Piskorz, Jaroslaw; Goslinski, Tomasz; Mielcarek, Jadwiga; Konopka, Krystyna; Düzgüne?, Nejat
The complete eradication of various targets, such as infectious agents or cancer cells, while leaving healthy host cells untouched, is still a great challenge faced in the field of medicine. Photodynamic therapy (PDT) seems to be a promising approach for anticancer treatment, as well as to combat various dermatologic and ophthalmic diseases and microbial infections. The application of liposomes as delivery systems for porphyrinoids has helped overcome many drawbacks of conventional photosensitizers and facilitated the development of novel effective photosensitizers that can be encapsulated in liposomes. The development, preclinical studies and future directions for liposomal delivery of conventional and novel photosensitizers are reviewed. PMID:23591149
Electronic properties of the interface between hexadecafluoro copper phthalocyanine and unsubstituted copper phthalocyanine films
Komolov, A. S., E-mail: firstname.lastname@example.com; Lazneva, E. F. [Saint Petersburg State University, Faculty of Physics (Russian Federation); Pshenichnyuk, S. A. [Russian Academy of Sciences, Institute of Molecular and Crystal Physics, Ufa Research Center (Russian Federation); Gavrikov, A. A.; Chepilko, N. S.; Tomilov, A. A.; Gerasimova, N. B.; Lezov, A. A.; Repin, P. S. [Saint Petersburg State University, Faculty of Physics (Russian Federation)
The formation of an interface during the deposition of unsubstituted copper phthalocyanine (CuPc) films on the surface of hexadecafluoro copper phthalocyanine (F{sub 16}-CuPc) films is studied. An incident low-energy electron beam with energies from 0 to 25 eV is used to test the surface under study according to the very-low-energy electron-diffraction technique (VLEED) in the mode of total current spectroscopy. For F{sub 16}-CuPc films, the structure of the maxima in the total current spectra and its main differences from the structure of the maxima for the CuPc film are determined in the energy range from 5 to 15 eV above the Fermi level. The differences in the structure of vacant electron orbitals for CuPc and F{sub 16}-CuPc are also revealed using density functional theory calculations. As a result of an analysis of variations in the intensities of the total current spectra of the CuPc and F{sub 16}-CuPc films, it is assumed that an intermediate layer up to 1 nm thick appears during the formation of an interface between these films, which is characterized by a spread of the features in the total current spectrum. The height, width, and change in the work function are determined for the studied F{sub 16}-CuPc/NuPc interface barrier. A decrease in the level of vacuum by 0.7 eV occurs in the boundary region, which corresponds to electron density transfer from the CuPc film toward the F{sub 16}-CuPc substrate.
XPS investigation of thionyl chloride action on iron phthalocyanines and naphthalocyanines and on hydrogen phthalocyanine — Correlations with the activity of Li/SOCl 2 cells
NASA Astrophysics Data System (ADS)
Savy, Michel; Riga, Joseph; Verbist, Jacques J.
X-ray photoelectron spectroscopic measurements have been performed on iron phthalocyanines and naphthalocyanines, and hydrogen phthalocyanine powders, after dissolution in SOCl 2 and reprecipitation. The comparison of XPS results with catalytic activities observed in the lithium/thionyl chloride batteries during their discharge underlines the rôles of the central ion oxidation facility and ligand stability in the electrocatalysis of SOCl 2 reduction.
Enhanced anticancer efficacy by ATP-mediated liposomal drug delivery.
Mo, Ran; Jiang, Tianyue; Gu, Zhen
A liposome-based co-delivery system composed of a fusogenic liposome encapsulating ATP-responsive elements with chemotherapeutics and a liposome containing ATP was developed for ATP-mediated drug release triggered by liposomal fusion. The fusogenic liposome had a protein-DNA complex core containing an ATP-responsive DNA scaffold with doxorubicin (DOX) and could release DOX through a conformational change from the duplex to the aptamer/ATP complex in the presence of ATP. A cell-penetrating peptide-modified fusogenic liposomal membrane was coated on the core, which had an acid-triggered fusogenic potential with the ATP-loaded liposomes or endosomes/lysosomes. Directly delivering extrinsic liposomal ATP promoted the drug release from the fusogenic liposome in the acidic intracellular compartments upon a pH-sensitive membrane fusion and anticancer efficacy was enhanced both in vitro and in vivo. PMID:24764317
DNA-binding and Oxidative Properties of Cationic Phthalocyanines and Their Dimeric Complexes with Anionic Phthalocyanines Covalently Linked to Oligonucleotides
A. A. Kuznetsova; E. A. Lukyanets; L. I. Solovyeva; D. G. Knorre; O. S. Fedorova
Design of chemically modified oligonucleotides for regulation of gene expression has attracted considerable attention over the past decades. One actively pursued approach involves antisense or antigene oligonucleotide constructs carrying reactive groups, many of these based on transition metal complexes. The complexes of Fe(II) and Co(II) with phthalocyanines are extremely good catalysts of oxidation of organic compounds with molecular oxygen and
Heterogeneous PNA Liposomes for Gene Delivery
NASA Astrophysics Data System (ADS)
Marques, Bruno; Morfesis, Ana; Yoon, Diana; Schneider, James
To circumvent complications of DNA adsorption onto cationic liposomes (i.e. structural reorganization, cytotoxicity), we have developed a liposomal system that binds genetic material via hydrogen bonding interactions. These liposomes contain surfactants linked to peptide nucleic acid (PNA), a synthetic DNA mimic with unique DNA-binding properties. We target multiple short regions of the DNA strand, sequestering the DNA from nuclease in solution, to protect it from nuclease digestion. Here, we present zeta potential measurements quantifying the extent of PNA incorporation in the liposomes, as well as the extent of DNA binding and nuclease activity under various conditions for mixtures of di- and trinucleotide PNA. We also discuss our attempts to identify the minimal PNA oligomer length to achieve stable binding and sequence specificity.
Nonphospholipid fluid liposomes with switchable photocontrolled release.
Cui, Zhong-Kai; Phoeung, Thida; Rousseau, Pierre-Antoine; Rydzek, Gaulthier; Zhang, Qian; Bazuin, C Geraldine; Lafleur, Michel
We created novel nonphospholipid photosensitive liposomes from a mixture of a monoacylated azobenzene amphiphile (AzoC10N(+)) and cholesterol sulfate (Schol). This system belongs to the family of sterol-enriched nonphospholipid liposomes that were shown to form stable large unilamellar vesicles (LUVs) with enhanced impermeability. Fluid bilayers were successfully prepared from AzoC10N(+)/Schol (25/75 molar ratio) mixtures, and LUVs could be derived at room temperature using standard extrusion methods. The isomerization process of the bilayer-inserted AzoC10N(+) was characterized. Leakage from these liposomes could be induced by the photoconversion of AzoC10N(+) from its trans form to its cis form. This photocontrolled release from fluid liposomes contrasts with the case of phospholipid-based azo-containing liposomes, which are generally required to be in the gel phase to be photosensitive. It is proposed that the very high degree of conformational order of the monoalkylated amphiphile and the tight packing of the hydrophobic core of the AzoC10N(+)/Schol liposomes make them responsive to the presence of the bulky cis azo isomer. Interestingly, the liposome impermeability could be fully restored by the photoisomerization of the cis form back to the trans form, providing a sharp on-and-off control of payload release. In addition, these nonphospholipid liposomes display a very limited passive release. Therefore, it is shown that AzoC10N(+)/Schol LUVs can be used as nanocontainers, whose content can be released by light in a controlled and switchable manner. PMID:25149436
Ehrlich tumor inhibition using doxorubicin containing liposomes.
Elbialy, Nihal Saad; Mady, Mohsen Mahmoud
Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, DOX in solution or DOX encapsulated within liposomes prepared from DMPC/CHOL/DPPG/PEG-PE (100:100:60:4) in molar ratio. Cytotoxicity assay showed that the IC50 of liposomes containing DOX was greater than that DOX only. Tumor growth inhibition curves in terms of mean tumor size (cm(3)) were presented. All the DOX formulations were effective in preventing tumor growth compared to saline. Treatment with DOX loaded liposomes displayed a pronounced inhibition in tumor growth than treatment with DOX only. Histopathological examination of the entire tumor sections for the various groups revealed marked differences in cellular features accompanied by varying degrees in necrosis percentage ranging from 12% for saline treated mice to 70% for DOX loaded liposome treated mice. The proposed liposomal formulation can efficiently deliver the drug into the tumor cells by endocytosis (or passive diffusion) and lead to a high concentration of DOX in the tumor cells. The study showed that the formulation of liposomal doxorubicin improved the therapeutic index of DOX and had increased anti-tumor activity against Ehrlich tumor models. PMID:25972739
Plasmon resonant liposomes for controlled drug delivery
NASA Astrophysics Data System (ADS)
Knights-Mitchell, Shellie S.; Romanowski, Marek
Nanotechnology use in drug delivery promotes a reduction in systemic toxicity, improved pharmacokinetics, and better drug bioavailability. Liposomes continue to be extensively researched as drug delivery systems (DDS) with formulations such as Doxil® and Ambisome® approved by FDA and successfully marketed in the United States. However, the limited ability to precisely control release of active ingredients from these vesicles continues to challenge the broad implementation of this technology. Moreover, the full potential of the carrier to sequester drugs until it can reach its intended target has yet to be realized. Here, we describe a liposomal DDS that releases therapeutic doses of an anticancer drug in response to external stimulus. Earlier, we introduced degradable plasmon resonant liposomes. These constructs, obtained by reducing gold on the liposome surface, facilitate spatial and temporal release of drugs upon laser light illumination that ultimately induces an increase in temperature. In this work, plasmon resonant liposomes have been developed to stably encapsulate and retain doxorubicin at physiological conditions represented by isotonic saline at 37o C and pH 7.4. Subsequently, they are stimulated to release contents either by a 5o C increase in temperature or by laser illumination (760 nm and 88 mW/cm2 power density). Successful development of degradable plasmon resonant liposomes responsive to near-infrared light or moderate hyperthermia can provide a new delivery method for multiple lipophilic and hydrophilic drugs with pharmacokinetic profiles that limit clinical utility.
Liposomal Formulation of Amphiphilic Fullerene Antioxidants
Zhou, Zhiguo; Lenk, Robert P.; Dellinger, Anthony; Wilson, Stephen R.; Sadler, Robert; Kepley, Christopher L.
Novel amphiphilic fullerene[70] derivatives that are rationally designed to intercalate in lipid bilayers are reported, as well as its vesicular formulation with surprisingly high loading capacity up to 65% by weight. The amphiphilic C70 bisadduct forms uniform and dimensionally stable liposomes with auxiliary natural phospholipids as demonstrated by buoyant density test, particle size distribution and 31P NMR. The antioxidant property of fullerenes is retained in the bipolarly functionalized C70 derivative, Amphiphilic Liposomal Malonylfullerene[70] (ALM) as well as in its liposomal formulations, as shown by both electron paramagnetic resonance (EPR) studies and in vitro reactive oxygen species (ROS) inhibition experiments. The liposomally formulated ALM efficiently quenched hydroxyl radicals and superoxide radicals. In addition, the fullerene liposome inhibited radical-induced lipid peroxidation and maintained the integrity of the lipid bilayer structure. This new class of liposomally formulated, amphipathic fullerene compounds represents a novel drug delivery system for fullerenes and provides a promising pathway to treat oxidative stress-related diseases. PMID:20839887
A Review on Composite Liposomal Technologies for Specialized Drug Delivery
Mufamadi, Maluta S.; Pillay, Viness; Choonara, Yahya E.; Du Toit, Lisa C.; Modi, Girish; Naidoo, Dinesh; Ndesendo, Valence M. K.
The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications. PMID:21490759
Liposomal palmitoyl-L-asparaginase: characterization and biological activity
Joăo C. S. Jorge; Roman Perez-Soler; José G. Morais; Maria Eugénia M. Cruz
A new derivative ofL-asparaginase, palmitoyl-L-asparaginase (palmitoyl-L-ASNase), has been incorporated in liposomes. For this purpose we modified the dehydration-rehydration method and optimized the liposomal composition. The pharmacokinetics, toxicity, and in vivo antitumor activity against P1534 lymphoma of different liposomal palmitoyl-L-ASNase formulations were studied. Liposomal encapsulation of palmitoyl-L-ASNase as compared with free palmitoyl-L-ASNase resulted in a prolongation of the blood half-life (from
Cobaltacarborane–phthalocyanine conjugates: Syntheses and photophysical properties
Li, Hairong; Fronczek, Frank R.; Vicente, M. Graça H.
Syntheses of two new cobaltacarborane–phthalocyanine conjugates, one anionic (Pc 6) and one zwitterionic (Pc 7), were accomplished via cyclotetramerization of the corresponding cobaltacarborane-substituted phthalonitriles (4 or 5) with excess phthalonitrile in quinoline. X-ray structures of two phthalonitrile precursors (2 and 3) were obtained and are discussed, and the absorption and emission properties of the two cobaltacarborane–phthalocyanine conjugates in several solvents were investigated. The anionic conjugate 6 exists mainly as a monomer in polar organic solvents and has fluorescence quantum yields in the region 0.2–0.3. The zwitterionic conjugate 7 aggregates in solution and displays lower quantum yields ~0.1 in organic solvents. PMID:20808725
Gas sensing mechanisms in chemiresistive metal phthalocyanine nanofilms
NASA Astrophysics Data System (ADS)
Bohrer, Forest I.
Chemiresistive films of metallophthalocyanines (MPcs; M = Fe, Co, Ni, Cu, Zn, and H2) are shown to be sensitive to gas phase electron donors and acceptors. The mechanism of sensing occurs through coordination of the analyte molecule to metal center of the phthalocyanine; electron donors cause film current losses by trapping of charge carriers, while electron acceptors causes current gains by generation of charge carriers within the film. Vapor phase peroxides may cause gains or losses of film current by electrocatalytic processes dependent on the metal center. MPcs featuring varied metal centers and peripheral substituents are prepared via literature procedures. A novel route is devised for synthesis of a copper phthalocyanine incorporating the 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) group. MPc films are deposited by organic molecular beam epitaxy (OMBE) and spin-coating; film morphologies are examined by atomic force microscopy (AFM). It is demonstrated that substrate temperature during OMBE deposition can significantly alter grain morphology. Spin-coating offers a cost-effective alternative to OMBE, with soluble, functionalized phthalocyanines. The roles of solvent and functional group are explored and procedures for preparing uniform amorphous films are described. The differing mechanisms of sensing in metal-free phthalocyanine (H 2Pc) and metalated phthalocyanines (MPc) are examined with respect to electron-donating (basic) analytes. MPc sensitivities to vapor phase electron donors are correlated exponentially with analyte basicity as described by binding enthalpy, consistent with the van't Hoff equation and the standard free energy of reaction. Coordination of analytes to the phthalocyanine metal center (MPc) or inner protons (H2Pc) is the dominant mechanism of chemical sensing for basic analytes. Sensor recovery times t90 are demonstrated to depend exponentially on binding enthalpy. Linear discriminant analysis is used to identify analytes. Single sensor normalization of analyte concentration leads to excellent discrimination and identification of analytes. MPc sensing arrays are shown to be redox-selective vapor sensors of hydrogen peroxide and di-t-butyl peroxide. These peroxides cause unique current losses in CoPc sensors and current gains in FePc, NiPc, CuPc, ZnPc, and H2Pc sensors. Detection limits of 50 ppb and 250 ppb are achieved for hydrogen peroxide and di-t-butyl peroxide, respectively. Oxidation and reduction of peroxides via catalysis at the phthalocyanine surface is consistent with the pattern of sensor responses. Differential analysis by redox contrast of a small array of sensors thus uniquely identifies peroxide vapors. Chemically sensitive field-effect transistors (ChemFETs) of ZnPc are evaluated for use as vapor sensors. The average carrier mobility is 1.3x10 -4 cm2 V-1 s-1, comparable to previously reported phthalocyanine mobility values. ZnPc ChemFETs display persistent photoconductivity, lasting up to 1.5 months, which induces significant baseline drift. Persistent photoconductivity and sensor instability require improvements to the ZnPc ChemFET architecture before its implementation as vapor sensors.
Organic photodetectors based on phthalocyanine and fullerenes: dielectric properties.
Sahu, Satyajit; Pal, Amlan J
Fabrication and characterization of organic photodetectors based on copper phthalocyanine and fullerenes are presented. We study current-voltage and impedance characteristics of the devices under dark and varied illumination conditions. The current-voltage characteristics in the reverse bias show little or no dark current and large photocurrent. The results show that photocurrent in the devices is associated with a decrease in bulk resistance and an increase in dielectric constant of the active material. PMID:19441333
Nanostructured copper phthalocyanine-sensitized multiwall carbon nanotube films.
Hatton, Ross A; Blanchard, Nicholas P; Stolojan, Vlad; Miller, Anthony J; Silva, S Ravi P
We report a detailed study of the interaction between surface-oxidized multiwall carbon nanotubes (o-MWCNTs) and the molecular semiconductor tetrasulfonate copper phthalocyanine (TS-CuPc). Concentrated dispersions of o-MWCNT in aqueous solutions of TS-CuPc are stable toward nanotube flocculation and exhibit spontaneous nanostructuring upon rapid drying. In addition to hydrogen-bonding interactions, the compatibility between the two components is shown to result from a ground-state charge-transfer interaction with partial charge transfer from o-MWCNT to TS-CuPc molecules orientated such that the plane of the macrocycle is parallel to the nanotube surface. The electronegativity of TS-CuPc as compared to unsubsubtituted copper phthalocyanine is shown to result from the electron-withdrawing character of the sulfonate substituents, which increase the molecular ionization potential and promote cofacial molecular aggregation upon drying. Upon spin casting to form uniform thin films, the experimental evidence is consistent with an o-MWCNT scaffold decorated with phthalocyanine molecules self-assembled into extended aggregates reminiscent of 1-D linearly stacked phthalocyanine polymers. Remarkably, this self-organization occurs in a fraction of a second during the spin-coating process. To demonstrate the potential utility of this hybrid material, it is successfully incorporated into a model organic photovoltaic cell at the interface between a poly(3-hexylthiophene):[6,6]-phenyl-C61 butyric acid methyl ester bulk heterojunction layer and an indium-tin oxide-coated glass electrode to increase the light-harvesting capability of the device and facilitate hole extraction. The resulting enhancement in power conversion efficiency is rationalized in terms of the electronic, optical, and morphological properties of the nanostructured thin film. PMID:17439261
Photoconductivity in Metal-Free Phthalocyanine Single Crystals
George H. Heilmeier; George Warfield
The spectral response of photoconductivity in metal-free phthalocyanine crystals was obtained in the region 2500–25 000 Ĺ, and was found to have the same response edges as the optical absorption spectrum. The correspondence between the valley-to-valley separation of the structure found in the strong response regions of the spectral response of photoconductivity and the peak-to-peak separation of the infrared optical
In vitro photodynamic therapy on melanoma cell lines with phthalocyanine
H. Kolarova; P. Nevrelova; R. Bajgar; D. Jirova; K. Kejlova; M. Strnad
Photodynamic therapy (PDT) is a new treatment modality of tumours. The photochemical interactions of sensitizer, light, and molecular oxygen produce singlet oxygen and other forms of active oxygen, such as peroxide, hydroxyl radical and superoxid anion. Phthalocyanine ClAlPcS2, belonging among the promising second generation of sensitizers, was tested as an inducer of photodamage. We report the production of reactive oxygen
ORIGINAL PAPER Encapsulation of ascorbic acid in liposomes prepared
Paris-Sud XI, Université de
ORIGINAL PAPER Encapsulation of ascorbic acid in liposomes prepared with milk fat globule membrane and bioavailability. Although liposomes are generally prepared with phospholipids from soy or egg, in recent years, and to evaluate their encapsulation behavior using ascorbic acid as a model biomolecule. Liposomes prepared
Biomolecular Science of Liposome-Nanoparticle , Stephen M. Anthony2
Granick, Steve
Biomolecular Science of Liposome-Nanoparticle Constructs Yan Yu1 , Stephen M. Anthony2 , Sung Chul by allowing nanoparticles to adsorb to the outer leaflet of liposomes, are found to be stabilized against with colloids of the conventional type. At the single- liposome level, the distribution of diffusion
Budding of Liposomes Role of Intrinsic Shape of Membrane Constituents
Iglic, Ales
CHAPTER 8 Budding of Liposomes Role of Intrinsic Shape of Membrane Constituents Ales Iglic1,Ă-Constituent Energy 255 3. Liposomes Composed of a Single Kind of Phospholipid Molecules 256 3.1. The two-state model of the pear shape and the ADE model 269 4. Spherical Budding in Liposomes Composed of Two Kinds of Molecules
Fluorescent Liposome Flow Markers for Microscale Particle-Image Velocimetry
Singh, Anup
Fluorescent Liposome Flow Markers for Microscale Particle-Image Velocimetry Anup K. Singh,* Eric B 94551-0969 Unilamellar liposomes carrying both encapsulated and surface-immobilized fluorophores have. The unilamellar liposomes were made with phospholipids and cholesterol by extru- sion through a polycarbonate
Stimuli-Responsive Liposome Fusion Mediated by Gold Nanoparticles
Zhang, Liangfang
Stimuli-Responsive Liposome Fusion Mediated by Gold Nanoparticles Dissaya Pornpattananangkul,, Sage, and diagnostic and imaging agents.1 Liposomes can carry both hydro- philic and hydrophobic agents with high ef functionalized with specific ligands that target liposomes and their pay- loads to the sites of action
Surface Potential of Charged Liposomes Determined by Second Harmonic Generation
Eisenthal, Kenneth B.
Articles Surface Potential of Charged Liposomes Determined by Second Harmonic Generation Yan Liu that the surface potential of charged liposomes can be determined by second harmonic generation. The Gouy charge density and the surface potential of liposomes consisting of the negatively charged phospholipid
Formation of Fibrinogen-Based Hydrogels Using Phototriggerable Diplasmalogen Liposomes
Formation of Fibrinogen-Based Hydrogels Using Phototriggerable Diplasmalogen Liposomes Zhi-Yi Zhang Manuscript Received December 4, 2001 We report the triggered release of Ca2+ from liposomal compartments to induce rapid gelation of protein-based hydrogels. Phototriggerable liposomes were designed by entrapping
Liposome division by a simple bacterial division machinery
Erickson, Harold P.
Liposome division by a simple bacterial division machinery Masaki Osawa ()1 and Harold P. Erickson not divide the thick-walled liposomes. Here we developed a unique system to observe Z rings in unilamellar that produced concave distortions when viewed at the equator of the liposome. When viewed en face at the top
Formation of homogeneous unilamellar liposomes from an interdigitated matrix
Gruner, Sol M.
Formation of homogeneous unilamellar liposomes from an interdigitated matrix Alla Polozovaa,*,1 gels. Further hydration of these gels results in the formation of liposomes whose morphology depends-phosphatidylcholine (POPC) and 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG), small homogeneous and unilamellar liposomes
Liposome technology. Volume III: Targeted drug delivery and biological interaction
Gregoriadis, G.
These three volumes cover liposome technology in pharmacology and medicine. Contributors emphasize methodology used in their own laboratories, and include a brief introduction, coverage of relevant literature, applications and critical evaluations for the methods they describe. In Volume III, the growing variety of techniques yielding targeted liposomes and approaches of studying liposomal behavior both in vitro and in vivo are discussed.
Review article Impact of liposomes as delivery systems
Paris-Sud XI, Université de
Review article Impact of liposomes as delivery systems in veterinary medicine Juan M. Sallovitz. Liposomes are lipid vesicles formed when phospoholipids are exposed to an aqueous environment. They arrange of the dispersion, and any substance dissolved in it, within the vesicle. Liposomes have remarkable features
Nanoengineered Structures for Holding and Manipulating Liposomes and Cells
Zare, Richard N.
Nanoengineered Structures for Holding and Manipulating Liposomes and Cells Clyde F. Wilson, Garth J exceptional stability in capturing, transporting, and releasing single cells and liposomes 1-12 µm in diameter subsequently probed by laser-induced fluorescence (LIF). In the second study, a single liposome containing car
Sterically Stabilized Liposomes: Improvements in Pharmacokinetics and Antitumor Therapeutic Efficacy
D. Papahadjopoulos; T. M. Allen; A. Gabizon; E. Mayhew; K. Matthay; S. K. Huang; K.-D. Lee; M. C. Woodle; D. D. Lasic; C. Redemann; F. J. Martin
The results obtained in this study establish that liposome formulations incorporating a synthetic polyethylene glycol-derivatized phospholipid have a pronounced effect on liposome tissue distribution and can produce a large increase in the pharmacological efficacy of encapsulated antitumor drugs. This effect is substantially greater than that observed previously with conventional liposomes and is associated with a more than 5-fold prolongation of
Phthalocyanines And Their Sulfonated Derivatives As Photosensitizers In Photodynamic Therapy.
NASA Astrophysics Data System (ADS)
Riesz, Peter; Krishna, C. Murali
Photodynamic therapy (PDT) of human tumors with hematoporphyrin derivative (HpD) has achieved encouraging results. However, HpD is a complex mixture whose composition varies in different preparations and with time of storage. The future promise of PDT for cancer treatment depends on the development of new chemically defined sensitizers which absorb more strongly than HpD in the 600-800 nm region. A shift to higher wavelengths is desirable since it allows increased light penetration in human tissues. In vivo, these sensitizers should be non-toxic, localize selectively in tumors and generate cytotoxic species upon illumination with a high quantum yield. These damaging species may be singlet oxygen (1O2) produced by the transfer of energy from the triplet state of the sensitizer to oxygen (Type II) or superoxide anion radicals formed by electron transfer to oxygen or substrate radicals generated by electron or hydrogen transfer directly from the sensitizer (Type I). The recent work of several groups indicating that phthalocyanines and their water soluble derivatives are promising candidates for PDT is reviewed. The photophysics, photochemistry, photosensitized killing of cultured mammalian cells and the use for in vivo photodynamic therapy of phthalocyanines is outlined. Our studies of the post-illumination photohemolysis of human red blood cells as a model system for membrane photomodification sensitized by phthalocyanine sulfonates are consistent with the predominant role of 1O2 as the damaging species.
In vitro photodynamic therapy on melanoma cell lines with phthalocyanine.
Kolarova, H; Nevrelova, P; Bajgar, R; Jirova, D; Kejlova, K; Strnad, M
Photodynamic therapy (PDT) is a new treatment modality of tumours. The photochemical interactions of sensitizer, light, and molecular oxygen produce singlet oxygen and other forms of active oxygen, such as peroxide, hydroxyl radical and superoxid anion. Phthalocyanine ClAlPcS(2), belonging among the promising second generation of sensitizers, was tested as an inducer of photodamage. We report the production of reactive oxygen species (ROS) and the phototoxicity of ClAlPcS(2) assessed using G361 melanoma cells. A semiconductor laser (lambda=675nm, output power 21mW) was used as a source for evocation of the photodynamic effect. ROS generation and H(2)O(2) release after PDT on G361 cells were detected using probe CM-H(2)DCFDA and recorded by luminescence spectrometer. Viability studies show, that the optimum phototoxic effect tested on G361 melanoma cells was determined in the combination of laser dose of 25Jcm(-2) and phthalocyanine ClAlPcS(2) concentration of 5microg/ml. This combination of phthalocyanine concentration and corresponding radiation dose was lethal for melanoma cells. PMID:17092686
Potentiality of double liposomes containing salmon calcitonin as an oral dosage form
Kenji Yamabe; Yoshinori Kato; Hiraku Onishi; Yoshiharu Machida
The hypocalcemic effects of salmon calcitonin (SCT) after oral administration in rats by means of SCT-loading double liposomes (DL) which consist of liposomes containing small liposomes were investigated. SCT-loading DL consisted of four types of the inner liposomes such as neutral liposomes (NL) and cationic charged liposomes (CL) prepared using Coatsome®, and neutral (VET) and cationic charged (c-VET) liposomes prepared
Surface Engineering of Liposomes for Stealth Behavior
Nag, Okhil K.; Awasthi, Vibhudutta
Liposomes are used as a delivery vehicle for drug molecules and imaging agents. The major impetus in their biomedical applications comes from the ability to prolong their circulation half-life after administration. Conventional liposomes are easily recognized by the mononuclear phagocyte system and are rapidly cleared from the blood stream. Modification of the liposomal surface with hydrophilic polymers delays the elimination process by endowing them with stealth properties. In recent times, the development of various materials for surface engineering of liposomes and other nanomaterials has made remarkable progress. Poly(ethylene glycol)-linked phospholipids (PEG-PLs) are the best representatives of such materials. Although PEG-PLs have served the formulation scientists amazingly well, closer scrutiny has uncovered a few shortcomings, especially pertaining to immunogenicity and pharmaceutical characteristics (drug loading, targeting, etc.) of PEG. On the other hand, researchers have also begun questioning the biological behavior of the phospholipid portion in PEG-PLs. Consequently, stealth lipopolymers consisting of non-phospholipids and PEG-alternatives are being developed. These novel lipopolymers offer the potential advantages of structural versatility, reduced complement activation, greater stability, flexible handling and storage procedures and low cost. In this article, we review the materials available as alternatives to PEG and PEG-lipopolymers for effective surface modification of liposomes. PMID:24300562
Liposomal Encapsulated Rhodomyrtone: A Novel Antiacne Drug
Chorachoo, Julalak; Amnuaikit, Thanaporn; Voravuthikunchai, Supayang P.
Rhodomyrtone isolated from the leaves of Rhodomyrtus tomentosa possesses antibacterial, anti-inflammatory, and anti-oxidant activities. Since rhodomyrtone is insoluble in water, it is rather difficult to get to the target sites in human body. Liposome exhibited ability to entrap both hydrophilic and hydrophobic compounds and easily penetrate to the target site. The present study aimed to develop a novel liposomal encapsulated rhodomyrtone formulations. In addition, characterization of liposome, stability profiles, and their antiacne activity were performed. Three different formulations of total lipid concentrations 60, 80, and 100??mol/mL were used. Formulation with 60??mol/mL total lipid (phosphatidylcholine from soybean and cholesterol from lanolin in 4?:?1, w/w) exhibited the highest rhodomyrtone encapsulation efficacy (65.47 ± 1.7%), average particle size (209.56 ± 4.8?nm), and ?-potential (–41.19 ± 1.3?mV). All formulations demonstrated good stability when stored for 2 months in dark at 4°C as well as room temperature. Minimal inhibitory concentration and minimal bactericidal concentration values of liposomal formulation against 11 clinical bacterial isolates and reference strains ranged from 1 to 4 and from 4 to 64??g/mL, respectively, while those of rhodomyrtone were 0.25–1 and 0.5–2??g/mL, respectively. The MIC and MBC values of liposome formulation were more effective than topical drugs against Staphylococcus aureus and Staphylococcus epidermidis. PMID:23762104
Remotely controlled diffusion from magnetic liposome microgels.
Hanuš, Jaroslav; Ullrich, Martin; Dohnal, Ji?í; Singh, Mandeep; St?pánek, František
The reversible, temperature-dependent change in the permeability of a phospholipid bilayer has been used for controlling the diffusion rate of encapsulated molecular payload from liposomes. Liposomes were preloaded with a fluorescent dye and immobilized in calcium alginate hydrogel microparticles that also contained iron oxide nanoparticles. The composite microparticles were produced by a drop-on-demand inkjet method. The ability of iron oxide nanoparticles to locally dissipate heat upon exposure to a radio-frequency (RF) alternating magnetic field was used to control the local temperature and therefore diffusion from the liposomes in a contactless way using an RF coil. Several different release patterns were realized, including repeated on-demand release. The internal structure of the composite alginate-liposome-magnetite microparticles was investigated, and the influence of microparticle concentration on the heating rate was determined. In order to achieve a temperature rise required for the liposome membrane melting, the concentration of alginate beads should be at least 25% of their maximum packing density for the nanoparticle concentration and specific absorption rate used. PMID:23461732
Structural analysis of zinc phthalocyanine (ZnPc) thin films: X-ray diffraction study
S. Senthilarasu; Y. B. Hahn; Soo-Hyoung Lee
X-ray diffraction (XRD) was used to analyze the structure of thermally evaporated zinc phthalocyanine (ZnPc) organic thin films, as functions of the substrate temperature and film thickness. A metastable alpha to stable beta phase transformation has been observed when the films are coated at higher substrate temperatures. The core structure of the zinc phthalocyanine macrocycle is formed by four isoindole
A combination of liposomal sunitinib plus liposomal irinotecan and liposome co-loaded with two drugs enhanced antitumor activity in PC12-bearing mouse.
Maitani, Yoshie; Saito, Hiroshi; Seishi, Yuki; Iwase, Yuko; Yamauchi, Takayasu; Higashiyama, Kimio; Sugino, Takashi
Pheochromocytomas are highly angiogenic neuroendocrine tumors. The side effects of treatment with cytotoxic agents frequently outweigh the benefits. Neuroendocrine tumors are highly angiogenic, dependent on vascular endothelial growth factor and receptor (VEGFR) activation. Sunitinib has antitumor and antiangiogenic activities that target VEGFRs. We investigated the antitumor activity of liposomal sunitinib and irinotecan alone and in combination. Liposomal sunitinib and irinotecan, and liposomes co-loaded with both drugs were prepared, and antitumor activity and biodistribution were examined in nude mice bearing PC12 tumors. Liposomal sunitinib increased in life span (ILS, 14.3%) compared with free sunitinib (-17.1% ILS) with moderate tumor growth suppression, whereas liposomal irinotecan suppressed tumor growth significantly without a survival benefit compared with free irinotecan (-21.7 and -13.3% ILSs, respectively). The combination of liposomal sunitinib plus liposomal irinotecan, and liposomes co-loaded with both drugs, induced significant inhibition of tumor growth and increased life-span more than the combination of free drugs. Accumulation of irinotecan in tumors by the combination of the two liposomal drugs and liposomes co-loaded with both drugs was significantly increased compared with the combination of free drugs. This study provides novel formulations of sunitinib and irinotecan in combination for the treatment of pheochromocytoma. PMID:23050928
Photodynamic inactivation of Aeromonas hydrophila by cationic phthalocyanines with different hydrophobicity.
Kussovski, Veselin; Mantareva, Vanya; Angelov, Ivan; Orozova, Petya; Wöhrle, Dieter; Schnurpfeil, Günter; Borisova, Ekaterina; Avramov, Latchezar
Antibacterial photodynamic therapy is a pioneering method for the inactivation of pathogenic bacteria. Four tetra alkyl-substituted cationic phthalocyanines with different hydrocarbon chains attached to the pyridyloxy group were synthesized. These photodynamic sensitizers were studied for antibacterial inactivation of a multidrug-resistant strain of Gram-negative bacterium Aeromonas hydrophila. Aeromonas species are recognized as etiological agents of a wide spectrum of diseases in humans and animals. The uptake of phthalocyanines by the bacterial cells decreased with an increase in cell density. Following the phthalocyanine solubility from hydrophilic to hydrophobic complexes, the accumulation capacity increased. Full inactivation was achieved with phthalocyanine with (methoxy) pyridyloxy substitution following a short exposure time, low drug concentration and mild irradiation. Although the phthalocyanine with the longest hydrocarbon chain (C12) has some toxic effect in the absence of light, substantial phototoxic effect was obtained with the optimal combination of drug-irradiation parameters. PMID:19431233
Mechanical properties of a giant liposome studied using optical tweezers
NASA Astrophysics Data System (ADS)
Shitamichi, Yoko; Ichikawa, Masatoshi; Kimura, Yasuyuki
The mechanical properties of a micrometer-sized giant liposome are studied by deforming it from the inside using dual-beam optical tweezers. As the liposome is extended, its shape changes from a sphere to a lemon shape, and finally, a tubular part is generated. The surface tension ? and the bending rigidity ? of the lipid membrane are obtained from the measured force-extension curve. In a one-phase liposome, it was found that ? increases as the charged component increases but ? remains approximately constant. In a two-phase liposome, the characteristic deformation and the force-extension curve differ from those observed for the one-phase liposome.
Accumulation, internalization and therapeutic efficacy of neuropilin-1-targeted liposomes
Paoli, Eric E.; Ingham, Elizabeth S.; Zhang, Hua; Mahakian, Lisa M.; Fite, Brett Z.; Gagnon, M. Karen; Tam, Sarah; Kheirolomoom, Azadeh; Cardiff, Robert D.; Ferrara, Katherine W.
Advancements in liposomal drug delivery have produced long circulating and very stable drug formulations. These formulations minimize systemic exposure; however, unfortunately, therapeutic efficacy has remained limited due to the slow diffusion of liposomal particles within the tumor and limited release or uptake of the encapsulated drug. Here, the carboxyl-terminated CRPPR peptide, with affinity for the receptor neuropilin-1 (NRP), which is expressed on both endothelial and cancer cells, was conjugated to liposomes to enhance the tumor accumulation. Using a pH sensitive probe, liposomes were optimized for specific NRP binding and subsequent cellular internalization using in vitro cellular assays. Liposomes conjugated with the carboxyl-terminated CRPPR peptide (termed C-LPP liposomes) bound to the NRP-positive primary prostatic carcinoma cell line (PPC-1) but did not bind to the NRP-negative PC-3 cell line, and binding was observed with liposomal peptide concentrations as low as 0.16 mol%. Binding of the C-LPP liposomes was receptor-limited, with saturation observed at high liposome concentrations. The identical peptide sequence bearing an amide terminus did not bind specifically, accumulating only with a high (2.5 mol%) peptide concentration and adhering equally to NRP positive and negative cell lines. The binding of C-LPP liposomes conjugated with 0.63 mol% of the peptide was 83-fold greater than liposomes conjugated with the amide version of the peptide. Cellular internalization was also enhanced with C-LPP liposomes, with 80% internalized following 3hr incubation. Additionally, fluorescence in the blood pool (~40% of the injected dose) was similar for liposomes conjugated with 0.63 mol% of carboxyl-terminated peptide and non-targeted liposomes at 24 hr after injection, indicating stable circulation. Prior to doxorubicin treatment, in vivo tumor accumulation and vascular targeting were increased for peptide-conjugated liposomes compared to non-targeted liposomes based on confocal imaging of a fluorescent cargo, and the availability of the vascular receptor was confirmed with ultrasound molecular imaging. Finally, over a 4-week course of therapy, tumor knockdown resulting from doxorubicin-loaded, C-LPP liposomes was similar to non-targeted liposomes in syngeneic tumor-bearing FVB mice and C-LPP liposomes reduced doxorubicin accumulation in the skin and heart and eliminated skin toxicity. Taken together, our results demonstrate that a carboxyl-terminated RXXR peptide sequence, conjugated to liposomes at a concentration of 0.63 mol%, retains long circulation but enhances binding and internalization, and reduces toxicity. PMID:24434424
Application of liposomes in drug development — focus on gastroenterological targets
Zhang, Jian-Xin; Wang, Kun; Mao, Zheng-Fa; Fan, Xin; Jiang, De-Li; Chen, Min; Cui, Lei; Sun, Kang; Dang, Sheng-Chun
Over the past decade, liposomes became a focal point in developing drug delivery systems. New liposomes, with novel lipid molecules or conjugates, and new formulations opened possibilities for safely and efficiently treating many diseases including cancers. New types of liposomes can prolong circulation time or specifically deliver drugs to therapeutic targets. This article concentrates on current developments in liposome based drug delivery systems for treating diseases of the gastrointestinal tract. We will review different types and uses of liposomes in the development of therapeutics for gastrointestinal diseases including inflammatory bowel diseases and colorectal cancer. PMID:23630417
Microfluidic-Enabled Liposomes Elucidate Size-Dependent Transdermal Transport
Junqueira, Mariana; Vreeland, Wyatt N.; Quezado, Zenaide; Finkel, Julia C.; DeVoe, Don L.
Microfluidic synthesis of small and nearly-monodisperse liposomes is used to investigate the size-dependent passive transdermal transport of nanoscale lipid vesicles. While large liposomes with diameters above 105 nm are found to be excluded from deeper skin layers past the stratum corneum, the primary barrier to nanoparticle transport, liposomes with mean diameters between 31–41 nm exhibit significantly enhanced penetration. Furthermore, multicolor fluorescence imaging reveals that the smaller liposomes pass rapidly through the stratum corneum without vesicle rupture. These findings reveal that nanoscale liposomes with well-controlled size and minimal size variance are excellent vehicles for transdermal delivery of functional nanoparticle drugs. PMID:24658111
Recent Trends of Polymer Mediated Liposomal Gene Delivery System
Lee, Sang-Soo; George Priya Doss, C.; Yagihara, Shin; Kim, Do-Young
Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD) blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole. PMID:25250340
Liposomes from hydrogenated soya lecithin formed in sintered glass pores.
Zawada, Zygmunt H
Possible complete closure of hydrophilic drug solutions in liposomes with required dimensions is the aim of variety liposome techniques. The ease of separating medication-loaded liposomes from liposome suspension to achieve an appropriate drug concentration in the final preparation is also desired. This paper describes the use of liposome preparation method, called reverse-phase evaporation, which leads to practical achievement of the earlier mentioned objectives. Preparation process is performed in an appropriately designed device. In optimal conditions of liposome preparation the final encapsulation efficiency of hydrophilic drug solution amounted to 50% in liposomes with a diameter in the range of a few micrometers up to 250 nm. The diameter of terminal liposomes is a simple function of relative amount of the lipid used and the degree of emulsion emulsification w/o at the beginning of liposome preparation. The density of the concentrated drug solution trapped in liposomes is usually higher than that of the buffer. Therefore, the loaded liposomes may be easily separated from non-trapped material by using of a simple sedimentation at 30000 x g. Density of aqueous drug solution insufficient to effective centrifugation can be magnified with an appropriate quantity of sucrose solution before encapsulation. PMID:22574513
Immunotargeting of Liposomes Containing Lipophilic Antitumor Prodrugs
Atsuhide Mori; Stephen J. Kennel; Leaf Huang
Potential therapeutic applications of recently developed liposomes with a reduced affinity to the reticuloendothelial systems and a prolonged circulation time as targeting systems for lipophilic prodrugs were examined. In these studies, liposomes composed of phosphatidylcholine and cholesterol, additionally containing monosialoganglioside (GM1) or polyethylene glycol conjugated to phosphatidyl-ethanolamine (PEG-PE), were used. Three antitumor lipophilic prodrugs, N-trifluoroacetyl-adriamycin-14-valerate (AD32), araC-diphosphate-diglyceride (araCdPdG), and 3',5'-o-dipalmitoyl-5-fluoro-2'-deoxyuridine
Liposomes for specific depletion of macrophages from organs and tissues.
van Rooijen, Nico; Hendrikx, Esther
A liposome mediated macrophage "suicide" approach has been developed, based on the liposome mediated internalization of the small hydrophilic molecule clodronate in macrophages J Leukoc Biol 62:702, 1997. This molecule has a very short half life when released in the circulation, but does not easily cross phospholipid bilayers of liposomes or cell membranes. As a consequence, once ingested by a macrophage in a liposome encapsulated form, it will be accumulated within the cell as soon as the liposomes are digested with the help of its lysosomal phospholipases. At a certain intracellular clodronate concentration, the macrophage is eliminated by apoptosis. Given the fact that, neither the liposomal phospholipids chosen, nor clodronate are toxic to other (non-phagocytic) cells, this method has proven its efficacy and specificity for depletion of macrophage subsets in various organs. In several cases, organ specific depletion can be obtained by choosing the right administration route for the clodronate liposomes. PMID:20072882
PUBLISHED ONLINE: 19 JANUARY 2014 | DOI: 10.1038/NPHYS2855 Liposome adhesion generates traction stress
Gardel, Margaret
ARTICLES PUBLISHED ONLINE: 19 JANUARY 2014 | DOI: 10.1038/NPHYS2855 Liposome adhesion generates. To address this, we directly measure the stresses generated during liposome adhesion. We find that liposome-sized liposomes as a simple model system to probe the extent to which liposome adhesion facilitates changes
Recognition and clearance of liposomes containing phosphatidylserine are mediated by serum opsonin
Dexi Liu; Feng Liu; Young K. Song
Liver uptake of liposomes containing phosphatidylserine was studied in a single pass liver perfusion system and found to be serum dependent. The effectiveness of serum in mediating liposome uptake by the liver depends on liposome size. Large liposomes appeared to be opsonized more efficiently and, therefore, taken up more by the liver than the smaller ones. The effects of liposome
Innovative Liposomes as a Transfollicular Drug Delivery System: Penetration into Porcine Hair Follicles
Sascha Jung; Nina Otberg; Gisela Thiede; Heike Richter; Wolfram Sterry; Steffen Panzner; Jürgen Lademann
Liposomes had been widely used for drug delivery in the past. In this study, five different liposomes were used as a follicular delivery system in pig ear skin. The liposomes mainly differed in their sphere diameter, lipid composition, and surface charge. A novel class of liposomes being amphoteric in their charge behavior are compared to established anionic and cationic liposomes.
Liposomal delivery and polyethylene glycol-liposomal oxaliplatin for the treatment of colorectal cancer (Review)
Oxaliplatin is effective for the treatment of advanced colorectal cancer; however, its application is restricted due to its dose-limiting toxicity. Liposomes are sphere-shaped vesicles consisting of one or more phospholipid bilayers. Liposomes as drug carriers are characterized by delayed release, lesion targeting and may be used as a drug-delivery system to decrease the side effects of cytotoxic drugs. Active targeting modification of liposomes may change the biological distribution of the anticancer agents, reduce or reverse multidrug resistance of tumor cells and enhance the effects of anticancer therapy. Based on the characteristics mentioned above, the aim of the present review was to demonstrate that polyethylene glycol-liposomes containing oxaliplatin may offer advantages for the treatment of colorectal cancer in clinical practice. PMID:24748970
Effective prodrug liposome and conversion to active metabolite.
Sadzuka, Y
Some antitumor agents encapsulated in liposomes have been used clinically. However, the usefulness of liposomes is limited to the liposomalization of active compounds. Irinotecan hydrochloride (CPT-11) is a prodrug of closed lactone ring form of SN-38, which is an active metabolite with antitumor and side toxicity. The plasma concentrations of closed CPT-11 and SN-38 increased with the liposomalization, and their blood circulation was prolonged by the polyethyleneglycol (PEG) modification. The antitumor activity of CPT-11 increased due to the elevated tumor distribution of closed CPT-11 and SN-38 levels by the PEG-modified liposomes. In the tumor, CPT-11 was converted to SN-38. Thus, it is considered that passive targeting to the tumor by liposomalization elevated the SN-38 level in the tumor especially and increased the antitumor activity of CPT-11. The closed/total ratio of SN-38 in the tumors of the liposomes group was greater than that of the CPT-11 solution group. Namely, SN-38 was thought to be generated in intact liposomes containing CPT-11. The generation of SN-38 in the liposomal membrane was shown after the incubation of liposome containing CPT-11 with carboxylesterase. It is therefore considered that part of CPT-11 is converted to SN-38 in intact liposomes. Furthermore, intestinal disorder, a side toxicity of CPT-11, decreased to depend on the closed SN-38 concentrations in the bile by liposomalization. Although the liposomes induce the improved tissue distribution of the prodrug, the tissue distribution of active metabolites do not always improve. However, CPT-11 entrapped liposome was useful. PMID:11467079
Nanocomposite liposomes containing quantum dots and anticancer drugs for bioimaging and therapeutic delivery: a comparison of cationic, PEGylated and deformable liposomes.
Wen, Chih-Jen; Sung, Calvin T; Aljuffali, Ibrahim A; Huang, Yu-Jie; Fang, Jia-You
Multifunctional liposomes loaded with quantum dots (QDs) and anticancer drugs were prepared for simultaneous bioimaging and drug delivery. Different formulations, including cationic, PEGylated and deformable liposomes, were compared for their theranostic efficiency. We had evaluated the physicochemical characteristics of these liposomes. The developed liposomes were examined using experimental platforms of cytotoxicity, cell migration, cellular uptake, in vivo melanoma imaging and drug accumulation in tumors. The average size of various nanocomposite liposomes was found to be 92–134 nm. Transmission electron microscopy confirmed the presence of QDs within liposomal bilayers. The incorporation of polyethylene glycol (PEG) and Span 20 into the liposomes greatly increased the fluidity of the bilayers. The liposomes provided sustained release of camptothecin and irinotecan. The cytotoxicity and cell migration assay demonstrated superior activity of cationic liposomes compared with other carriers. Cationic liposomes also showed a significant fluorescence signal in melanoma cells after internalization. The liposomes were intratumorally administered to a melanoma-bearing mouse. Cationic liposomes showed the brightest fluorescence in tumors, followed by classical liposomes. This signal could last for up to 24 h for cationic nanosystems. Intratumoral accumulation of camptothecin from free control was 35 nmol g(?1); it could be increased to 50 nmol g(?1) after loading with cationic liposomes. However, encapsulation of irinotecan into liposomes did not further increase intratumoral drug accumulation. Cationic liposomes were preferable to other liposomes as nanocarriers in both bioimaging and therapeutic approaches. PMID:23867977
Synthesis, characterization and spectral properties of novel zinc phthalocyanines derived from C2 symmetric diol
NASA Astrophysics Data System (ADS)
Gök, Ya?ar; Gök, Halil Zeki
In this study, we described the syntheses of new zinc(II) phthalocyanine compounds derived from (1R,2R)-1,2-diphenyl-1,2-ethanediol units. The phthalonitrile precursors 3 and 4 were synthesized by the reaction of 4,5-dichlorophthalonitrile with (1R,2R)-1,2-diphenyl-1,2-ethanediol. The synthesis of zinc(II) phthalocyanine 5 and zinc(II) phthalocyanine polymer 6 by cyclotetramerization of corresponding phthalonitrile derivative were accomplished in the presence of Zn(CH3CO2)2 in a Schlenk tube containing quinoline under nitrogen atmosphere. The zinc(II) phthalocyanine 5 showed enhanced solubility in various organic solvents. The aggregation behavior of phthalocyanines was investigated at different concentrations in different solvents. Both phthalocyanines were found to exist in non-aggregated form at concentrations between 10 × 10-6 and 1 × 10-6 mol dm-3. As the concentration increased to 5 × 10-5 mol dm-3, a deviation from ideality was observed for both phthalocyanines. The novel compounds were characterized by a combination of elemental analysis and 1H NMR, 13C NMR, IR, UV-Vis and MS spectral data.
Liposomal Conjugates for Drug Delivery to the Central Nervous System
Helm, Frieder; Fricker, Gert
Treatments of central nervous system (CNS) diseases often fail due to the blood–brain barrier. Circumvention of this obstacle is crucial for any systemic treatment of such diseases to be effective. One approach to transfer drugs into the brain is the use of colloidal carrier systems—amongst others, liposomes. A prerequisite for successful drug delivery by colloidal carriers to the brain is the modification of their surface, making them invisible to the reticuloendothelial system (RES) and to target them to specific surface epitopes at the blood–brain barrier. This study characterizes liposomes conjugated with cationized bovine serum albumin (cBSA) as transport vectors in vitro in porcine brain capillary endothelial cells (PBCEC) and in vivo in rats using fluorescently labelled liposomes. Experiments with PBCEC showed that sterically stabilized (PEGylated) liposomes without protein as well as liposomes conjugated to native bovine serum albumin (BSA) were not taken up. In contrast, cBSA-liposomes were taken up and appeared to be concentrated in intracellular vesicles. Uptake occurred in a concentration and time dependent manner. Free BSA and free cBSA inhibited uptake. After intravenous application of cBSA-liposomes, confocal fluorescence microscopy of brain cryosections from male Wistar rats showed fluorescence associated with liposomes in brain capillary surrounding tissue after 3, 6 and 24 h, for liposomes with a diameter between 120 and 150 nm, suggesting successful brain delivery of cationized-albumin coupled liposomes. PMID:25835091
Liposome disposition in vivo. VI: Delivery to the lung
Abra, R.M.; Hunt, C.A.; Lau, D.T.
The effect of negatively charged liposome components and vesicle size on the time course and dose dependency of liposome disposition in mice was studied with a view to optimizing liposome delivery to the lung. The disposition of large multilamellar liposomes was followed using 125I-labeled p-hydroxybenzamidine phosphatidyl ethanolamine. Of the three negatively charged liposome compositions studied (phosphatidyl choline-X-cholesterol-alpha-tocopherol, molar ratio: 4:1:5:0.1; X . phosphatidyl serine, dipalmitoyl phosphatidic acid, or phosphatidyl glycerol), phosphatidyl serine liposomes resulted in the greatest accumulation in lungs. Lung levels decreased up to 95 h postdose, at which time 6% of the liposome dose present at 2 h still remained. The disposition of phosphatidyl serine-containing liposomes was independent of dose for the range 0.04-21 mumol/animal. When liposomes containing phosphatidyl choline were prepared using a variety of extrusion and dialysis conditions, a strong link between liposome size and lung accumulation was revealed. A maximum lung accumulation of 30.9% of the administered dose was achieved with no detectable gross pathological lung lesions up to 24 h postdose.
The fluorescence and dynamics properties in phenoxy-phthalocyanines liquid
NASA Astrophysics Data System (ADS)
Yao, Cheng-Bao; Yan, Xiao-Yan; Tan, Ming-Yue; Li, Jin; Sun, Wen-Jun; Yang, Shou-Bin
We investigated the one/two-photon fluorescence and excited state dynamics properties of two synthesized phenoxy-phthalocyanines (Pc1 and Pc2) using mild reaction coordination method. The results show that the fast decay component in the time-resolved fluorescence technique dynamics comes from the intramolecular vibrational relaxation, the slower ones from the internal conversion. Furthermore, in comparison with one-photon fluorescence spectra, the red shift of two-photon fluorescence spectra can be explained by the reabsorption effect of molecules. The samples are expected to be a potential candidate for optical applications and photodynamic therapy.
Spectroscopic and microscopic investigations of phthalocyanine aggregates on Gold(111)
NASA Astrophysics Data System (ADS)
Nishida, Krista Rachel Akiko
Self-assembled organic pi systems are of interest because of their potential applications in light harvesting and electron transfer. Phthalocyanines (Pc) demonstrate desirable photonic and electronic properties, thus making them excellent candidates for functional nanostructures. The specific focus of this research has been the nanoscale aggregation of a metal-free organic dye, tetrasulfonic acid phthalocyanine (TSPc) and includes the use of UV-visible Spectroscopy, Resonance Light Scattering Spectroscopy (RLS), X-ray Photoelectron Spectroscopy (XPS), Atomic Force Microscopy (AFM) and ambient and ultra-high-vacuum Scanning Tunneling Microscopy (STM) and Scanning Tunneling Spectroscopy (STS). The UV-visible absorption studies show that TSPc aggregates upon dissolution in water and obeys Beer's Law within the concentration range of 10 -7M to 10-4M, indicating that TSPc concentration has no further effect on aggregation in aqueous solution. In addition, both ionic strength in NaCl and pH changes in the presence of NaOH, HCl or acetic acid (HAc) do affect aggregation. The RSL studies confirm these effects of pH only in the presence of HAc. The XPS studies show that the ratio of non-protonated to protonated nitrogens does not change with decreasing solution pH. STM images of TSPc deposited from pH<1 solutions reveal ordered branched web-like assemblies hundreds of nanometers in length, generally 2 nm tall and having variable widths. STM imaging shows TSPc aggregates decrease in order as pH increases. STM images of TSPc deposited from solutions with pH>10 show monolayer coverage of TSPc in salt form. High-resolution UHV-STM images of TSPc aggregates deposited from pH 0 solution on Au(111) reveal detailed coherent columnar architecture with the phthalocyanine macrocycles orientated parallel to the substrate surface. OMTS was used to identify the HOMO and LUMO of the TSPc aggregates and the results are contrasted with the same molecular states in unsubstituted metallated phthalocyanines (MPc). The positions of the filled and the empty states of the TSPc are comparable to those of other unsubstituted MPc's indicating that the electronegative sulfonate substituents have minimal effect on the electronic properties of the macrocycle. The HOMO-LUMO separation of TSPc is slightly above 2 eV, a value consistent with the literature assignments for the Pc ring band gap.
Intramolecular coupling in metal-free binuclear phthalocyanines
NASA Astrophysics Data System (ADS)
Dodsworth, E. S.; Lever, A. B. P.; Seymour, P.; Leznoff, C. C.
The electronic absorption and emission spectra of a series of mononuclear and binuclear metal-free phthalocyanine species are reported. The binuclear species are linked through a benzene ring by a bridge of 0,1,2,4 or 5 atoms. The spectroscopic data for the binuclear species, are analysed in terms of exciton coupling between the two halves of the molecule. Intramolecular coupling is seen to depend upon the nature of the bridging link. In some cases a cofacial conformation is possible; this gives rise to characteristic long-lived emission near 750 nm.
Characterization of Polymerized Liposomes Using a Combination of dc and Cyclical Electrical Field-Flow Fractionation
Utah, University of
Characterization of Polymerized Liposomes Using a Combination of dc and Cyclical Electrical Field Information ABSTRACT: Characterization of polymerized liposomes (PolyPIPosomes) was carried out using polymerized liposomes are used to demonstrate the applicability of the system to biomedical samples
Application of Antibody and Fluorophore-Derivatized Liposomes to Heterogeneous Immunoassays for D-dimer
Kilpatrick, Peter K.
Application of Antibody and Fluorophore-Derivatized Liposomes to Heterogeneous Immunoassays for D Carolina State University, Raleigh, North Carolina 27695-7905 Small unilamellar liposomes comprised functionalized with antibodies. The liposomes were conjugated with thousands of fluorescein molecules and 10
Application of phthalocyanines in flow- and sequential-injection analysis and microfluidics systems: A review.
van Staden, Jacobus Koos Frederick
Phthalocyanines and metallophthalocyanines play a very important role in the metabolism of living organisms through biological pigments or biochromes and are therefore also employed in numerous applications in analytical chemistry. In flow-, and sequential-injection analysis and microfluidic systems the role of phthalocyanines and metallophthalocyanines is centered as either that of analyte or that of a reagent or modifier in the determination of other species. This paper covers the attributes of phthalocyanines and metallophthalocyanines complexes as enhancements in chemical analysis in flow- and sequential injection analysis and microfluidic systems and points out the advantages and disadvantages in the implementation thereof. PMID:25882411
Orientation studies of Si-phthalocyanine sulfonic acids cast on SiOx substrates
NASA Astrophysics Data System (ADS)
Appel, G.; Ade, H.; Guerek, A. G.; Stadler, S.; Mikalo, R. P.; Schmeisser, D.
Layers of dihydroxy silicon phthalocyanine tetrasulfonic acid and oligo-?-oxo silicon phthalocyanine tetrasulfonic acid were prepared by solution-casting methods. The purity of the material was checked by X-ray photoemission spectroscopy. The orientation of the molecules in respect to the substrate plane was investigated by angle-dependent near-edge X-ray absorption fine-structure spectroscopy. The morphology was characterized by atomic force microscopy. Most samples exhibited a significant orientation that was accompanied by crystalline structures; others had no orientation at all with a dominant amorphous morphology. This behavior indicates that several preparation parameters affect the crystallinity and the orientation of the phthalocyanines.
Titanium and Ruthenium Phthalocyanines for NO2 Sensors: A Mini-Review
Paoletti, Anna Maria; Pennesi, Giovanna; Rossi, Gentilina; Generosi, Amanda; Paci, Barbara; Albertini, Valerio Rossi
This review presents studies devoted to the description and comprehension of phenomena connected with the sensing behaviour towards NO2 of films of two phthalocyanines, titanium bis-phthalocyanine and ruthenium phthalocyanine. Spectroscopic, conductometric, and morphological features recorded during exposure to the gas are explained and the mechanisms of gas-molecule interaction are also elucidated. The review also shows how X-ray reflectivity can be a useful tool for monitoring morphological parameters such as thickness and roughness that are demonstrated to be sensitive variables for monitoring the exposure of thin films of sensor materials to NO2 gas. PMID:22346697
The effect of lipid composition and liposome size on the release properties of liposomes-in-hydrogel.
Hurler, Julia; Žakelj, Simon; Mravljak, Janez; Pajk, Stane; Kristl, Albin; Schubert, Rolf; Škalko-Basnet, Nataša
To study the release of liposome-associated drugs into hydrogels, we designed and synthesized two pH-sensitive rhodamine derivatives to use as model compounds of different lipophilicities. The dyes were fluorescent when in the free form released from liposomes into the chitosan hydrogel, but not when incorporated within liposomes. The effect of liposomal composition, surface charge and vesicle size on the release of those incorporated dyes was evaluated. The lipophilicity of the rhodamine derivatives affected both the amount and rate of release. While liposome size had only a minor effect on the release of dyes into the hydrogel, the surface charge affected the release to a greater extent. By optimizing the characteristics of liposomes we could develop a liposomes-in-hydrogel system for application in wound therapy. We further characterized liposomes-in-hydrogel for their rheological properties, textures and moisture handling, as well as their potential to achieve a controlled release of the dye. The polymer-dependent changes in the hydrogel properties were observed upon addition of liposomes. The charged liposomes exhibited stronger effects on the textures of the chitosan hydrogels than the neutral ones. In respect to the ability of the system to handle wound exudates, chitosan-based hydrogels were found to be superior to Carbopol-based hydrogels. PMID:23994014
Investigating the Stability of eLiposomes at Elevated Temperatures.
Husseini, Ghaleb A; Pitt, William G; Javadi, Marjan
eLiposomes encapsulate a perfluorocarbon nanoemulsion droplet inside a liposome. Ultrasound is then used as a trigger mechanism to vaporize the perfluorocarbon, break the liposome, and release the desired drug to the tumor tissue. The purpose of this research is to show that eLiposomes synthesized using perfluoropentane are stable above the normal boiling point of the perfluoropentane and at body temperature and thus has potential for use in vivo. Experiments involving the release of fluorescent calcein molecules were performed on eLiposomes to measure the release of calcein at various temperatures in the absence of ultrasound. Results showed that eLiposomes are stable at body temperatures and that as the temperature increases above 40°C, calcein release from these novel nanocarriers increases. PMID:25261070
Polymorphism of DNAanionic liposome complexes reveals hierarchy of ion-mediated interactions
Harries, Daniel
Polymorphism of DNAanionic liposome complexes reveals hierarchy of ion-mediated interactions). Although synthetic nonviral systems such as cationic liposomes generally transfect less efficiently than
Acyclovir Liposomes for Intranasal Systemic Delivery: Development and Pharmacokinetics Evaluation
Ibrahim A. Alsarra; Amel Y. Hamed; Fars K. Alanazi
Intranasal route is one of the most attractive routes for dis- tributing drugs to systemic circulation. Liposomes are used as bio- compatible carriers to improve delivery properties across nasal mucosa. The objective of the present study was to formulate acy- clovir liposomes and partition into poly-N-vinyl-2-pyrrolidone. Entrapment efficiency showed that multilamellar and unilamel- lar liposomes were 43.2% ± 0.83 and
Ferrous sulfate liposomes: preparation, stability and application in fluid milk
Shuqin Xia; Shiying Xu
The effects of cholesterol and Tween 80 on the physical stability of empty liposomes were investigated. Results showed that the physical stability of liposomes, including electrostatic and steric stability, was improved by addition of cholesterol and Tween 80. Liposomes prepared by different methods, thin-film hydration, thin-film sonication, reverse-phase evaporation and freeze-thawing, were tested for their capacity to encapsulate ferrous sulfate.
Hemolytic properties of miltefosine in liposomes of various lipid compositions
M. V. Zhukova; O. V. Romanenko; V. A. Nikolaevich; M. A. Kisel'
The hemolytic activity of hexadecylphosphocholine (HePC) included in liposomes of phosphatidylcholine (PC), phosphatidylethanol\\u000a (PET), and their mixture in various ratios has been studied. Spectroscopic data suggest that supramolecular particles containing\\u000a less than 15% HePC occur as liposomes. Hemolysis at the same HePC concentration is less pronounced for liposomes (10% HePC)\\u000a than for micelles (30% HePC). The inclusion of anionic phosphatidylethanol
Liposomes as nanoreactors for the photochemical synthesis of gold nanoparticles.
Gudlur, Sushanth; Sandén, Camilla; Matoušková, Petra; Fasciani, Chiara; Aili, Daniel
A simple and novel method for the photochemical synthesis of AuNPs in liposomes is described. Gold salt is co-encapsulated with the photoinitiator Irgacure-2959 in POPC liposomes prepared via traditional thin-film hydration technique. UVA irradiation for 15min results in encapsulated AuNPs of 2.8±1.6nm in diameter that are primarily dispersed in the aqueous interior of the liposomes. PMID:26125517
Preparation and characterization of lyophilized liposomes with incorporated quercetin.
Alexopoulou, Elena; Georgopoulos, Aristidis; Kagkadis, Konstantinos A; Demetzos, Costas
Liposomes composed of egg-phosphatidylcholine (EPC) incorporating quercetin (QR) were prepared by the thin-film hydration method (TFHM) and the monophase solution method (MSM). A rapid and slow freeze-drying process was applied for both laboratory and industrial scales. The purpose of this study was to compare the two methods of liposome preparation, and further determine whether the lyophilization process affects the liposome physicochemical characteristics (size, polydispersity index, and ?-potential) and incorporation of quercetin. PMID:16556547
Endocytosis and intracellular processing accompanying transfection mediated by cationic liposomes
Daniel S Friend; Demetrios Papahadjopoulos; Robert J Debs
Cationic liposomes mediate efficient transfection of mammalian cells, but the manner in which cells internalize and process cationic liposome-DNA complexes has not been well characterized. We exposed several cell types, including human and murine erythroleukemia cells, African green monkey kidney cells (CV-1), isolated rat alveolar type II cells and alveolar macrophages to DNA-cationic liposome complexes containing N-(1-2,3-dioleyloxypropyl)-N,N,N-triethylammonium (DOTMA) and Dioleylphosphatidylethanolamine
Pesticide detection with a liposome-based nano-biosensor
Vicky Vamvakaki; Nikos A. Chaniotakis
Monitoring of the organophosphorus pesticides dichlorvos and paraoxon at very low levels has been achieved with liposome-based nano-biosensors. The enzyme acetylcholinesterase was effectively stabilized within the internal nano-environment of the liposomes. Within the liposomes, the pH sensitive fluorescent indicator pyranine was also immobilized for the optical transduction of the enzymatic activity. Increasing amounts of pesticides lead to the decrease of
Liposome-mediated DNA vaccination: the effect of vesicle composition
Yvonne Perrie; Peter M. Frederik; Gregory Gregoriadis
Liposome-entrapped DNA has been shown to enhance the potency of DNA vaccines, possibly by facilitating uptake of the plasmid by antigen-presenting cells (APC). In this paper, we have investigated the influence of the liposomal composition and surface charge on such potency. Plasmid DNA pRc\\/CMV HBS encoding the S (small) region of hepatitis B surface antigen was entrapped within cationic liposomes
pH-triggered echogenicity and contents release from liposomes.
Nahire, Rahul; Hossain, Rayat; Patel, Rupa; Paul, Shirshendu; Meghnani, Varsha; Ambre, Avinash H; Gange, Kara N; Katti, Kalpana S; Leclerc, Estelle; Srivastava, D K; Sarkar, Kausik; Mallik, Sanku
Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the cellular lysosomes has been successfully used to enhance the rate for releasing contents. However, imparting pH sensitivity to liposomes requires the synthesis of specialized lipids with structures that are substantially modified at a reduced pH. Herein, we report an alternative strategy to render liposomes pH sensitive by encapsulating a precursor which generates gas bubbles in situ in response to acidic pH. The disturbance created by the escaping gas bubbles leads to the rapid release of the encapsulated contents from the liposomes. Atomic force microscopic studies indicate that the liposomal structure is destroyed at a reduced pH. The gas bubbles also render the liposomes echogenic, allowing ultrasound imaging. To demonstrate the applicability of this strategy, we have successfully targeted doxorubicin-encapsulated liposomes to the pancreatic ductal carcinoma cells that overexpress the folate receptor on the surface. In response to the decreased pH in the lysosomes, the encapsulated anticancer drug is efficiently released. Contents released from these liposomes are further enhanced by the application of continuous wave ultrasound (1 MHz), resulting in substantially reduced viability for the pancreatic cancer cells (14%). PMID:25271780
Increased Liposome Extravasation in Selected Tissues: Effect of Substance P
NASA Astrophysics Data System (ADS)
Rosenecker, Joseph; Zhang, Weiming; Hong, Keelung; Lausier, James; Geppetti, Pierangelo; Yoshihara, Shigemi; Papahadjopoulos, Demetrios; Nadel, Jay A.
We have used a pharmacologic mediator to open intercellular connections in selected vessels to allow liposomes to escape from the blood stream and to extravasate into tissues that have appropriate receptors. We have examined the effects of substance P (SP), a peptide known to increase vascular permeability in selected tissues, such as trachea, esophagus, and urinary bladder in rats. We used quantitative fluorescence analysis of tissues to measure two fluorescent markers, one attached to the lipid (rhodamine-phosphatidylethanolamine) and another, doxorubicin (an antitumor drug), encapsulated within the aqueous interior. We have also examined the deposition of liposomes microscopically by the use of encapsulated colloidal gold and silver enhancement. Analysis of the biochemical and morphological observations indicate the following: (i) Injection of SP produces a striking increase in both liposome labels, but only in tissues that possess receptors for SP in postcapillary venules; (ii) liposome material in these tissues has extravasated and is found extracellularly near a variety of cells beyond the endothelial layer over the first few hours; (iii) 24 h following injection of liposomes and SP, liposome material is found in these tissues, localized intracellularly in both endothelial cells and macrophages. We propose that appropriate application of tissue-specific mediators can result in liposome extravasation deep within tissues that normally do not take up significant amounts of liposomes from the blood. Such liposomes are able to carry a variety of pharmacological agents that can be released locally within selected target tissues for therapeutic purposes.
Complexation-triggerable liposome mixed with silk protein and chitosan.
Hong, Yeon-Ji; Kim, Jin-Chul
Complexation-triggerable liposomes were prepared by modifying the surface of egg phosphatidylcholine (EPC) liposomes with hydrophobicized silk fibroin (HmSF) and hydrophobicized chitosan (HmCh). Maximum complexation, determined by measuring the diameter of complexation, was found when the ratio of HmSF to HmCh was 14:1, so they were immobilized on the surface of liposomes at the same ratio. The degree of fluorescence quenching of calcein in liposomal suspension was as high as 68% when the ratio of surface modifier (HmSF + HmCh) to EPC was 1:15. When the ratio was increased to 1:5, the degree of quenching decreased to 32%, indicating the inefficient formation of liposome. Liposome mixed with the surface modifier was multi-lamellar vesicle on TEM photo. And, the mean diameter was larger than those of liposome mixed with either HmSF or HmCh, possibly due to insoluble complex on the liposomal surface. The liposome exhibited a pH-sensitive release and triggered the release at pH 5.5 and 6.0. It is believed that complexation is responsible for the promoted release at those pH values. PMID:26059216
Modifying the release properties of liposomes toward personalized medicine.
Cipolla, David; Wu, Huiying; Gonda, Igor; Eastman, Simon; Redelmeier, Tom; Chan, Hak-Kim
Surfactant-liposome interactions have historically been investigated as a simplified model of solubilization and breakdown of biological membranes by surfactants. In contrast, our goal was to utilize surfactants to modify the encapsulation and release properties of liposomes. The ability to manufacture one liposomal formulation, which could be modified by the addition of a surfactant to support a wide range of release profiles, would provide greater flexibility than manufacturing multiple batches of liposomes, each differing in composition and with its own specific release profile. A liposomal ciprofloxacin formulation was modified by the addition of various surfactants. These formulations were characterized in terms of liposome structure by cryo-TEM imaging, vesicle size by dynamic light scattering, drug encapsulation by centrifugation-filtration, and in vitro release (IVR) performance. The addition of polysorbate 20 or polysorbate 80 to liposomal ciprofloxacin, in a hypotonic environment, resulted in a concentration-dependent loss of encapsulated drug, and above 0.4% polysorbate 20, or 0.2% polysorbate 80, a modified IVR profile as well. This study demonstrates that the encapsulation and release properties of a liposomal formulation can be modified postmanufacture by the addition of judiciously chosen surfactants in combination with osmotic swelling of the liposomes and may support a personalized approach to treating patients. PMID:24715635
Heteroleptic naphthalo-phthalocyaninates of lutetium: synthesis and spectral and conductivity properties.
Dubinina, Tatiana V; Kosov, Anton D; Petrusevich, Elizaveta F; Maklakov, Sergey S; Borisova, Nataliya E; Tomilova, Larisa G; Zefirov, Nikolay S
Novel heteroleptic naphthalo-phthalocyaninates of lutetium possessing a symmetrical substituted naphthalocyanine deck were synthesized on the basis of two preformed synthetic blocks: naphthalocyanine ligand and lutetium phthalocyaninates. The compounds obtained were characterized by (1)H NMR and high-resolution MALDI-TOF/TOF mass spectrometry. The correlation between the nature of the substituents and the spectral properties of the target complexes was determined by the introduction of electron-donating (aryl-, aryloxy-) or electron-withdrawing (chloro-) substituents into the phthalocyanine deck. In addition, the nature of peripheral substituents was shown not to affect drastically the phthalocyanine conductivity and activation energy. Conductivity properties depend on thin film morphology which, in turn, relies on intermolecular ?-? interactions. PMID:25826576
Highly positive-charged zinc(II) phthalocyanine as non-aggregated and efficient antifungal photosensitizer.
Li, Xing-Shu; Guo, Jun; Zhuang, Jing-Jing; Zheng, Bi-Yuan; Ke, Mei-Rong; Huang, Jian-Dong
A new tetra-?-substituted zinc(II) phthalocyanine containing dodeca-amino groups (compound 4) and its quaternized analogue (compound 5) have been prepared and evaluated for their photoactivities against Candida albicans. Compared with the dodeca-amino phthalocyanine 4, the dodeca-cationic phthalocyanine 5 exhibits a higher photodynamic inactivation against C. albicans with an IC90 value down to 1.46 ?M, which can be attributed to its non-aggregated nature in aqueous environments and more efficient cellular uptake. More interestingly, 5 shows a higher photodynamic inactivation on C. albicans due to its stronger affinity to C. albicans cells than mammalian cells. These results suggest that the highly positive-charged phthalocyanine 5 is a potential non-aggregated antifungal photosensitizer, which shows some selectivity toward the fungus. PMID:25911302
Spectroscopic insights on imidazole substituted phthalocyanine photosensitizers: Fluorescence properties, triplet state and singlet oxygen generation
NASA Astrophysics Data System (ADS)
Zhang, Xian-Fu; Lin, Yong; Guo, Wenfeng; Zhu, Jingzhong
Imidazole substituted metal phthalocyanine (Pc) complexes were synthesized. UV-vis absorption, steady state and time-resolved fluorescence, as well as laser flash photolysis were used to measure the photophysical and photosensitizing properties. All the imidazole-phthalocyanine conjugates show high ?T (quantum yield of excited triplet formation), high ?? (singlet oxygen formation yield, >0.50) and good fluorescence properties (quantum yield ?f > 0.20 and lifetime ?f > 3.0 ns). Compared to the unsubstituted Pc, both ?- and ?-imidazole substitutions result in the remarkable decrease in ?f and ?f, but the ?-substitution is stronger. The imidazole substitution, on the other hand, causes the increase of ?T, ?T, and ?? values. Magnesium phthalocyanine (MgPc) is more susceptible to the substitution than zinc phthalocyanine (ZnPc). The mechanism responsible for the result is suggested based on the involvement of intramolecular photoinduced electron transfer. The high ?? and appropriate fluorescence properties make the Pcs good candidate for PDT photosensitizers.
Antitumor activity of liposomal glucocorticoids: The relevance of liposome-mediated drug delivery, intratumoral localization and systemic activity
Ewelina Kluza; Sin Yuin Yeo; Sophie Schmid; Renate W. Boekhoven; Raymond M. Schiffelers; Gert Storm; Gustav J. Strijkers; Klaas Nicolay
Tumor-associated inflammation has been recognized as an important tumor growth propagator and, therefore, represents an attractive target for anti-cancer therapy. In the current study, inspired by recent findings on the anti-tumor activity of liposomal glucocorticoids, we introduce paramagnetic and fluorescent liposomes, encapsulating prednisolone phosphate (PLP), to evaluate the local delivery of liposomal glucocorticoids to the tumor and its importance for
Encapsulation of doxorubicin in liposomes containing phosphatidylethanol. Part I: Physicochemical characterization and antitumor activity of liquid crystal liposomes
M. V. Zhukova; M. A. Kisel'; B. B. Kuz'mitskii; A. E. Mashkovich; V. M. Nasek; O. V. Romanenko; S. G. Spivak
The effect of phosphatidylethanol (PE) anions on the incorporation of doxorubicin into liquid crystal liposomes consisting\\u000a of soybean phosphatidylcholine (PC) was studied. Over 90% of the antibiotic are encapsulated in liposomes in the case of a\\u000a PC\\/PE = 3: 2 molar ratio, with a doxorubicin content reaching 130 ?g\\/(mg phospholipids). The Stokes radius of the antibiotic-containing\\u000a liposomes is estimated at
Antitumor activity of liposome encapsulated fluoroorotic acid as a single agent and in combination with liposome irinotecan
Kareen Riviere; Heidi M. Kieler-Ferguson; Katherine Jerger; Francis C. Szoka
To test the hypothesis that co-delivery of synergistic drug combinations in the same liposome provides a better anti-tumor effect than the drugs administered in separate liposomes, fluoroorotic acid (FOA) alone and in combination with irinotecan (IRN) were encapsulated in liposomes and evaluated for their anti-tumor activity in the C26 colon carcinoma mouse model. A new chaotropic loading strategy was devised
Communication: Influence of graphene interlayers on the interaction between cobalt phthalocyanine and Ni(111)
NASA Astrophysics Data System (ADS)
Uihlein, Johannes; Peisert, Heiko; Glaser, Mathias; Polek, Ma?gorzata; Adler, Hilmar; Petraki, Fotini; Ovsyannikov, Ruslan; Bauer, Maximilian; Chassé, Thomas
The influence of graphene interlayers on electronic interface properties of cobalt phthalocyanine on Ni(111) is studied using both photoemission and X-ray absorption spectroscopy. A charge transfer associated with a redistribution of the d-electrons at the Co-atom of the phthalocyanine occurs at the interface to Ni(111). Even a graphene buffer layer cannot prevent the charge transfer at the interface to Ni(111); however, the detailed electronic situation is different.
Effects of germanium addition to copper phthalocyanine/fullerene-based solar cells
NASA Astrophysics Data System (ADS)
Oku, Takeo; Kumada, Kazuma; Suzuki, Atsushi; Kikuchi, Kenji
Copper phthalocyanine/fullerene-based solar cells were fabricated, and the electronic and optical properties were investigated. Effects of germanium addition to the solar cells were also investigated, which resulted in increase of power conversion efficiencies of the solar cells. Nanostructures of the solar cells were investigated by transmission electron microscopy and electron diffraction, which indicated formation of Ge compound nanoparticles in the copper phthalocyanine layers. Energy levels of the solar cells were discussed from the present analysis data.
Copper phthalocyanine as corrosion inhibitor for ASTM A606-4 steel in 16% hydrochloric acid
I. V. Aoki; I. C. Guedes; S. L. A. Maranhăo
A study based on the corrosion inhibition properties of copper phthalocyanine is described. Coverage degrees of copper phthalocyanine (Cu-phcy) on ASTM-A606-4 steel, obtained by weight loss measurements, were fitted to Langmuir, Frumkin, Temkin and Flory–Huggins adsorption isotherms. A better fit to the Langmuir isotherm was obtained. The polarization curves showed that polarization of both the anodic and cathodic reactions were
Hydrogen sensitive Schottky barriers in metal-copper phthalocyanine junctions and their photovoltaic effect
N. Yamamoto; S. Tonomura; H. Tsubomura
The photovoltaic and rectification properties of junctions of copper phthalocyanine (CuPc) with metals—Pd, Pt, Au, Cu, In, Al, and Mg—are investigated. Current-voltage characteristics are explained by the p-type nature of copper phthalocyanine that gives rise to a Schottky barrier, which changes with the metal work function. The action spectrum of the photovoltaic effect suggests that the light absorbed only in
Improvement of the efficiency of phthalocyanine organic Schottky solar cells with ITO electrode treatment
C. Y. Kwong; A. B. Djuriši?; P. C. Chui; L. S. M. Lam; W. K. Chan
The devices investigated in this work consisted of an indium tin oxide (ITO)-coated glass substrate, phthalocyanine (Pc) layer and an aluminum electrode. The Schottky cell exhibits optimal performance with one ohmic and one barrier contact. The work function of the ITO film is typically around 4.5–4.8 eV, while the HOMO level of phthalocyanine films is typically around 5.2 eV. It is known
Liposomal alendronate for the treatment of restenosis.
Gutman, Dikla; Golomb, Gershon
The current treatment for coronary restenosis following balloon angioplasty involves the use of a mechanical or drug eluting stent (DES). The advent of DES systems has effectively allayed much of the challenge of restenosis that has plagued the success of percutaneous coronary interventions (PCI). However, there are certain limitations to DES use, among which is late stent thrombosis. Innate immunity and inflammation are of major importance in the overreaction of the wound healing response to PCI-induced vascular injury, which leads to restenosis. Liposomes containing alendronate have been shown to deplete circulating monocytes and reduce experimental restenosis. This review presents a unique systemic approach for treating restenosis with alendronate liposomal nano-carriers and reports on its formulation development, formulation variables affecting monocyte/macrophage targeting, pharmacokinetics (PK) and biodistribution, in vitro and in vivo anti-inflammatory effect, and the recent results of the phase II clinical trial. PMID:22178594
Effect of lipid composition and liposome size on toxicity and in vitro fungicidal activity of liposome-intercalated amphotericin B.
Szoka, F C; Milholland, D; Barza, M
Intercalation of amphotericin B into liposomes at a 10 mol% drug/lipid ratio decreased its cytotoxicity by 3- to 90-fold in cultured murine cells and reduced its lethality by 2- to 8-fold in a median lethal dose (LD50) test in mice when compared with the commercial deoxycholate-solubilized drug (LD50 = 2.3 mg/kg). The cytotoxicity and lethality of the liposomal preparations were a function of their lipid composition and diameter. There was no correlation between the reduction of toxicity in the tissue culture assay and the reduction of lethality in the LD50 test. The rank order of reduction of lethality was sterol-containing liposomes greater than solid liposomes greater than fluid liposomes. In general, small sterol-containing vesicles were less lethal than large vesicles of the same composition. Intercalation of amphotericin B in sterol or solid liposomes increased not only the LD50 but also the time to death. The organ distribution of amphotericin B 24 h after intravenous administration was similar whether the drug was given as the commercial deoxycholate preparation or in liposomes. Finally, there were no differences among any of the formulations in their fungicidal activity against Candida tropicalis and Saccharomyces cerevisiae in vitro. The lesser and slower lethality of the liposomal and detergent-solubilized drug suggests that the mechanism by which liposomes reduce the lethality of amphotericin B is by slowing its rate of transfer to a sensitive cellular target. PMID:3579259
PEGylated Liposomes as Carriers of Hydrophobic Porphyrins.
Dzieciuch, Monika; Rissanen, Sami; Szyd?owska, Natalia; Bunker, Alex; Kumorek, Marta; Jamróz, Dorota; Vattulainen, Ilpo; Nowakowska, Maria; Róg, Tomasz; Kepczynski, Mariusz
Sterically stabilized liposomes (SSLs) (PEGylated liposomes) are applied as effective drug delivery vehicles. Understanding the interactions between hydrophobic compounds and PEGylated membranes is therefore important to determine the effectiveness of PEGylated liposomes for delivery of drugs or other bioactive substances. In this study, we have combined fluorescence quenching analysis (FQA) experiments and all-atom molecular dynamics (MD) simulations to study the effect of membrane PEGylation on the location and orientation of 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (p-THPP) that has been used in our study as a model hydrophobic compound. First, we consider the properties of p-THPP in the presence of different fluid phosphatidylcholine bilayers that we use as model systems for protein-free cell membranes. Next, we studied the interaction between PEGylated membranes and p-THPP. Our MD simulation results indicated that the arrangement of p-THPP within zwitterionic membranes is dependent on their free volume, and p-THPP solubilized in PEGylated liposomes is localized in two preferred positions: deep within the membrane (close to the center of the bilayer) and in the outer PEG corona (p-THPP molecules being wrapped with the polymer chains). Fluorescence quenching methods confirmed the results of atomistic MD simulations and showed two populations of p-THPP molecules as in MD simulations. Our results provide both an explanation for the experimental observation that PEGylation improves the drug-loading efficiency of membranes and also a more detailed molecular-level description of the interactions between porphyrins and lipid membranes. PMID:25965670
Mechanism of Oligonucleotide Release from Cationic Liposomes
Olivier Zelphati; Francis C. Szoka
We propose a mechanism for oligonucleotide (ODN) release from cationic lipid complexes in cells that accounts for various observations on cationic lipid-nucleic acid-cell interactions. Fluorescent confocal microscopy of cells treated with rhodamine-labeled cationic liposome\\/fluorescein-labeled ODN (F-ODN) complexes show the F-ODN separates from the lipid after internalization and enters the nucleus leaving the fluorescent lipid in cytoplasmic structures. ODN displacement from
Phthalocyanine photosensitizers as contrast agents for in vivo photoacoustic tumor imaging
Attia, Amalina Bte Ebrahim; Balasundaram, Ghayathri; Driessen, Wouter; Ntziachristos, Vasilis; Olivo, Malini
There is a need for contrast agents for non-invasive diagnostic imaging of tumors. Herein, Multispectral Optoacoustic Tomography (MSOT) was employed to evaluate phthalocyanines commonly used in photodynamic therapy as photoacoustic contrast agents. We studied the photoacoustic activity of three water-soluble phthalocyanine photosensitizers: phthalocyanine tetrasulfonic acid (PcS4), Zn(II) phthalocyanine tetrasulfonic acid (ZnPcS4) and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) in phantom and in tumor-bearing mice to investigate the biodistribution and fate of the phthalocyanines in the biological tissues. PcS4 was observed to grant good contrast between the different reticuloendothelial organs and accumulate in the tumor within an hour of post-administration. ZnPcS4 and AlPcS4 offered little contrast in photoacoustic signals between the organs. PcS4 is a promising photoacoustic contrast agent and can be exploited as a photodiagnostic agent. PMID:25780748
Photophysical property of a polymeric nanoparticle loaded with an aryl benzyl ester silicon (IV) phthalocyanine
NASA Astrophysics Data System (ADS)
Pan, Sujuan; Ma, Dongdong; Chen, Xiuqin; Wang, Yuhua; Yang, Hongqin; Peng, Yiru
Because of their excellent near-infrared (NIR) optical properties, phthalocyanines (Pcs) have been regarded as promising therapy agents for fluorescence image-guided drug delivery and noninvasive treatment of tumors by photodynamic therapy (PDT). Nevertheless, phthalocyanines are substantially limited in clinical applications owing to their poor solubility, aggregation and insufficient selectivity for cancer cells. To address these issues, we have developed a novel dendrimer-based theranostic nanoparticle for tumor-targeted delivery of phthalocyanine. The preparation procedure involved the modification of the silicon (IV) phthalocyanine molecule with a dendritic axially substitution, which significantly enhances their photophysical property. In order to improve biocompatibility and tumor-targeted delivery, the hydrophobic dendritic phthalocyanine was encapsulated by diblock amphiphilic copolymer poly (ethylene glycol)-poly (Epsilon-caprolactone) (MPEG-PCL) to form a polymeric nanoparticle. The polymeric nanoparticle is spherical with a diameter at about 90 nm. The photophysical property of the polymeric nanoparticle was studied by UV/Vis and fluorescence spectroscopic methods. Compared with the free dendritic phthalocyanine, the Q band of the polymeric nanoparticle was red-shifted, and the fluorescence intensity decreased. Furthermore, the polymeric nanoparticle has a relatively high loading amount and encapsulation rate. Therefore, the polymeric nanoparticle would be a promising third-generation photosensitizer (PS) for PDT.
Molecular interactions in imatinib-DPPC liposomes.
Béni, Szabolcs; Budai, Marianna; Noszál, Béla; Gróf, Pál
Imatinib (Gleevec) is a novel chemotherapeutic agent against Bcr-Abl protein tyrozine kinase, playing a crucial role in the therapy of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). Our study aimed at designing a liposomal imatinib formulation and investigating molecular interactions between lipid and imatinib, within the liposomal membrane. Multilamellar (MLV) and small unilamellar (SUV) vesicles were prepared from alpha-L-dipalmitoyl-phosphatidylcholine (DPPC). The effect of imatinib on the DPPC membrane was studied by electron paramagnetic resonance (EPR) spectroscopy and differential scanning calorimetry (DSC), at pH 5.2 and 9.0, where imatinib is in monocationic and neutral form, respectively. Our results indicate that imatinib interacts mainly with the DPPC head groups, leading to a slight increase in the mobility of the polar headgroups in case of MLVs. Contrary to that, imatinib causes a significant decrease in the fluidity of SUVs, which can be the result of a pH-dependent fusion/fission effect. The size distribution and morphology of liposomes were checked by dynamic light scattering and freeze-fracture electron microscopy. Our results direct attention to investigate the interactions of imatinib with artificial/biological membranes. PMID:16289747
Phototriggerable Liposomes: Current Research and Future Perspectives
Puri, Anu
The field of cancer nanomedicine is considered a promising area for improved delivery of bioactive molecules including drugs, pharmaceutical agents and nucleic acids. Among these, drug delivery technology has made discernible progress in recent years and the areas that warrant further focus and consideration towards technological developments have also been recognized. Development of viable methods for on-demand spatial and temporal release of entrapped drugs from the nanocarriers is an arena that is likely to enhance the clinical suitability of drug-loaded nanocarriers. One such approach, which utilizes light as the external stimulus to disrupt and/or destabilize drug-loaded nanoparticles, will be the discussion platform of this article. Although several phototriggerable nanocarriers are currently under development, I will limit this review to the phototriggerable liposomes that have demonstrated promise in the cell culture systems at least (but not the last). The topics covered in this review include (i) a brief summary of various phototriggerable nanocarriers; (ii) an overview of the application of liposomes to deliver payload of photosensitizers and associated technologies; (iii) the design considerations of photoactivable lipid molecules and the chemical considerations and mechanisms of phototriggering of liposomal lipids; (iv) limitations and future directions for in vivo, clinically viable triggered drug delivery approaches and potential novel photoactivation strategies will be discussed. PMID:24662363
Integration of ?-carotene molecules in small liposomes
NASA Astrophysics Data System (ADS)
Andreeva, Atanaska; Popova, Antoaneta
The most typical feature of carotenoids is the long polyene chain with conjugated double bonds suggesting that they can serve as conductors of electrons, acting as ''molecular wires'', important elements in the molecular electronic devices. Carotenoids are essential components of photosynthetic systems, performing different functions as light harvesting, photoprotection and electron transfer. They act also as natural antioxidants. In addition they perform structural role stabilizing the three-dimensional organization of photosynthetic membranes. Carotenoids contribute to the stability of the lipid phase, preserving the membrane integrity under potentially harmful environmental conditions. Carotenoids can be easily integrated into model membranes, facilitating the investigation of their functional roles. In carotenoid-egg phosphatidylcholine (EPC) liposomes ß-carotene is randomly distributed in the hydrocarbon interior of the bilayer, without any preferred, well defined orientation and retains a substantial degree of mobility. Here we investigate the degree of integration of ß-carotene in small unilamellar EPC liposomes and the changes in ß-carotene absorption and Raman spectra due to the lipid-pigment interaction. All observed changes in ß-carotene absorption and Raman spectra may be regarded as a result of the lipid-pigment interactions leading to the polyene geometry distortion and increasing of the environment heterogenety in the liposomes as compared to the solutions.
Liposomes by quasielastic light scattering and spectroturbidimetry
NASA Astrophysics Data System (ADS)
Khlebtsov, Boris N.; Khlebtsov, Nikolai G.; Shchyogolev, Sergei Y.
A variant of the experimental implementation of the quasi- elastic light scattering (QELS) method for determining the average particle size in liposome suspensions in the homodyne mode was considered. The aim of the investigations was to compare the data obtained with the result of a version of the method of spectroturbidimetry (STM) previously developed to determine the size and shell thickness of liposomes. For determination of the corresponding correlation functional, an experimental setup was used that was base don a helium-neon laser with a computer sound card as the analog-digital converter. Monodisperse suspension of latexes and colloidal gold as well as E. coli cell suspension were used as the test objects. The tests showed good accuracy of the QELS determination of the particle diameter d in the region of d < 100. Below this boundary, the accuracy of the particle size determination is limited by the relatively low resolving capacity of the analog-digital converter of the given type. It was established that the results of the determination of the average particle size in liposome polydisperse suspension obtained by QELS and STM were in satisfactory agreement.
Mannosylated liposomes for bio-film targeting.
Vyas, S P; Sihorkar, Vaibhav; Jain, Sanyog
Vesicular systems in general are investigated to achieve bacterial bio-film targeting as their architecture mimics bio-membranes in terms of structure and bio-behavior. This paper elaborates upon the role of the inherent characteristics of the carrier system and further envisages the role of anchored ligands in navigating the contents in the vicinity of bio-films. Vesicles in the present study were coated with hydrophobic derivatives of mannan (cholesteryl mannan and sialo-mannan). The prepared vesicles were characterized for size, shape, percentage entrapment and ligand binding specificity and results were compared with the uncoated versions. Using a set of in vitro and in vivo models, the bio-film targeting potential of plain and mannosylated liposomal formulations were compared. Results suggested that mannosylated vesicles could be effectively targeted to the model bacterial bio-films, compared with plain vesicles. Moreover, the sialo-mannan coated liposomes recorded superior targetability as reflected in the significantly higher percentage growth inhibition when compared with cholesteryl mannan coated liposomes. The engineered systems thus have the potential use for the delivery of anti-microbial agents to the bio-films. PMID:16997519
Liposomal nanoparticles as a drug delivery vehicle against osteosarcoma
NASA Astrophysics Data System (ADS)
Dhule, Santosh Subhashrao
The delivery of curcumin, a broad-spectrum anticancer drug, has been explored in the form of liposomal nanoparticles to treat osteosarcoma (OS). Curcumin is water insoluble and an effective delivery route is through encapsulation in cyclodextrins followed by a second encapsulation in liposomes. Liposomal curcumin's potential was evaluated against cancer models of mesenchymal (OS) and epithelial origin (breast cancer). The resulting 2-Hydroxypropyl-gamma-cyclodextrin/curcumin - liposome complex shows promising anticancer potential both in vitro and in vivo against KHOS OS cell line and MCF-7 breast cancer cell line. An interesting aspect is that liposomal curcumin initiates the caspase cascade that leads to apoptotic cell death in vitro in comparison with DMSO-curcumin induced autophagic cell death. In addition, the efficiency of the liposomal curcumin formulation was confirmed in vivo using a xenograft OS model. Curcumin-loaded gamma-cyclodextrin liposomes indicate significant potential as delivery vehicles for the treatment of cancers of different tissue origin. The second part of this study examines the anti-tumor potential of curcumin and C6 ceramide (C6) against osteosarcoma cell lines when both are encapsulated in the bilayer of liposomal nanoparticles. Curcumin in combination with C6 showed 1.5 times enhanced cytotoxic effect in the case of MG-63 and KHOS OS cell lines, in comparison with systems with curcumin alone. Interestingly, C6-curcumin liposomes were found to be less toxic on untransformed human cells in comparison to OS cell lines. In addition, cell cycle assays on a KHOS cell line after treatment revealed that curcumin only liposomes induced G 2/M arrest by upregulation of cyclin B1, while C6 only liposomes induced G1 arrest by downregulation of cyclin D1. C6-curcumin liposomes induced G2/M arrest and showed a combined effect in the expression levels of cyclin D1 and cyclin B1. Using pegylated liposomes to increase the plasma half-life and tagging with folate for targeted delivery in vivo, a significant reduction in tumor size was observed with C6-curcumin-folate liposomes. The encapsulation of two water insoluble drugs, curcumin and C6, in the lipid bilayer of liposomes enhances the cytotoxic effect and validates the potential of combined drug therapy.
Electrical properties of iodine-doped nickel (phthalocyanine) films
NASA Astrophysics Data System (ADS)
Nakamura, Shuhei; Ozaki, Tamon; Sawa, Goro; Amatatsu, Hiroshi; Yamaguchi, Shinji
The change in electrical conductivity of a vacuum evaporated nickel phthalocyanine (Ni(Pc) film with doping of iodine has been studied based upon the analyses of the film structure, electronic spectroscopy, and electron spin resonance measurements. It was found that an abrupt increment of electrical conductivity at the first stage of incremental doping is accompanied by a phase transition from a monoclinic system to a tetragonal system. This phase transition causes cracks on the surface of film and leads to the collapse of the polycrystalline structure upon further doping. It is concluded that a gentle increase in the electrical conductivity with further doping is limited by the competitive process between the increment of charge carriers and the decrement of the electrical conduction path, and a collapse of the polycrystalline structure due to a phase transition.
Hybrid structures of polycationic aluminum phthalocyanines and quantum dots.
Maksimov, E G; Gvozdev, D A; Strakhovskaya, M G; Paschenko, V Z
Semiconductor nanocrystals (CdSe/ZnS quantum dots, QDs) were used as inorganic focusing antenna, allowing for the enhancement of fluorescence and photosensitizing activity of polycationic aluminum phthalocyanines (PCs). It was found that QDs form stable complexes with PCs in aqueous solutions due to electrostatic interactions. In such hybrid complexes, we observed highly efficient nonradiative energy transfer from QD to PC, leading to a sharp increase in the effective absorption cross section of PC in the absorption bands of the CdSe/ZnS quantum dots. When hybrid complexes are excited within these bands, the intensity of PC fluorescence and the rate of photosensitized singlet oxygen generation increases significantly (up to 500 and 350%, correspondingly) compared to free PC at the same concentration. The observed effect is of interest for modeling primary stages of photosynthesis and increasing photosensitizing activity of dyes used in photodynamic therapy. PMID:25761686
Spectroscopic properties of phthalocyanine dyes for optical recording medium
NASA Astrophysics Data System (ADS)
Shen, Shuyin; Liu, Kai; Xu, Huijun; Gu, Donghong; Tang, Fulong; Chen, Qiying
Phthalocyanine dyes with various central metal atoms and different substituents showing improved spectroscopic properties to match the output of GaAs diode-laser have been synthesized. Smooth thin films have been prepared by spin- coating technique. Solvent-vapor induced crystallization of VOPc(OC3H7)4 has also been studied. The results showed that the VOPc(OC3H7)4 primarily deposited on glass substrate as an amorphous form. However, the dyes were changed to crystalline form by exposure to appropriate solvent vapors. The polymorphs of the VOPc(OC3H7)4 were investigated by visible absorption and IR spectroscopy, X-ray diffraction and high resolution electron microscopy. The optical recording performances of the thin films were also reported.
Nonlinear Optothermal Properties of Metal-Free Phthalocyanine
NASA Technical Reports Server (NTRS)
Abdeldayem, Hossin A.; Frazier, Donald O.; Penn, Benjamin G.; Smith, David D.; Banks, Curtis E.
The nonlinear optical properties of metal-free phthalocyanine (MFPC) thin films were examined using the second harmonic at 532 nm from a pulsed Nd:YAG laser, and the cw He-Ne , and Ar+ lasers. The He-Ne laser transmission at fixed input intensity was found to increase temporally within a time scale of twelve hours. The origin of this temporal change of transmission is discussed. The third order nonlinear susceptibilities (chi (exp(3))) by four-wave mixing were measured for films of different thickness. The saturation intensity of MFPC, and its absorption cross section, at 633 nm from a He-Ne laser, are reported. An optical bistability was recorded using a He-Ne laser. An AND logic gate was also demonstrated in the system. These phenomena in the system are attributed to refractive index modulation by thermal excitations.
Anomalous photoelectric emission from Ag on zinc-phthalocyanine film
Tanaka, Senku, E-mail: email@example.com [Department of Electric and Electronic Engineering, Faculty of Science and Engineering, Kinki University, Higashiosaka 577-8502 (Japan); Otani, Tomohiro; Fukuzawa, Ken; Hiromitsu, Ichiro [Department of Physics and Materials Science, Graduate School of Science and Engineering, Shimane University, Matsue 690-8504 (Japan); Ogawa, Koji; Azuma, Junpei; Yamamoto, Isamu; Takahashi, Kazutoshi; Kamada, Masao [Synchrotron Light Application Center, Saga University, Saga 840-8502 (Japan)
Photoelectric emission from organic and metal thin films is generally observed with irradiation of photon energy larger than 4?eV. In this paper, however, we report photoelectric emission from Ag on a zinc-phthalocyanine (ZnPc) layer at a photon energy of 3.4?eV. The threshold energy for this photoelectric emission is much smaller than the work function of Ag estimated by conventional photoelectron spectroscopy. The photoelectric emission by low-energy photons is significant for Ag thicknesses of less than 1?nm. Photoelectron spectroscopy and morphological study of the Ag/ZnPc suggest that the anomalous photoelectric emission from the Ag surface is caused by a vacuum level shift at the Ag/ZnPc interface and by surface plasmons of the Ag nanoparticles.
Optical limiting processes in derivatized fullerenes and porphyrins/phthalocyanines
Kohlman, R.; Klimov, V.; Shi, X. [and others
The authors review their results from spectral studies of the ultrafast excited-state absorption in fullerenes and derivatized fullerenes. These results allow determination of both the spectral response of reverse saturable absorption (RSA) nonlinearities such as optical limiting (OL) in fullerenes, and the dynamical response for different morphologies. The authors have investigated the effects of thin film and various sol-gel glass environments on the nanosecond OL and femtosecond dynamics of derivatized fullerenes. These data provide evidence of decay pathways which compete with the intersystem crossing to a triplet from the initial singlet states. With appropriate processing, however, the OL response of derivatized-fullerene sol-gel glasses can be enhanced to approach that of the same molecule in solution, while significantly enhancing the optical damage threshold. The optical limiting of these derivatized fullerenes is compared with that of various porphyrin and phthalocyanine molecules.
Antibacterial Efficacy of Benzoyl Peroxide in Phospholipid Liposomes
J. W. Fluhr; O. Barsom; W. Gehring; M. Gloor
Background: Literature reports indicate that phospholipid liposomes facilitate the accumulation of active agents in the infundibulum. Objective: The study hypothesis of an improved antibacterial efficacy of benzoyl peroxide (BPO) in phospholipid liposomes was tested in comparison with a commercial and a pharmacopoeial BPO preparation. Methods: The infundibular bacterial samples were obtained with the Permabond technique from 20 acne patients who
Antileishmanial and trypanocidal activities of new miltefosine liposomal formulations.
Papagiannaros, A; Bories, C; Demetzos, C; Loiseau, P M
Liposomes composed of hexadecylphosphocholine/egg phosphatidylcholine/stearylamine (HePC/EPC/SA) 10:10:0.1, 10:10:0.5 and 10:10:1 (molar ratio) (1-3) were prepared and lyophilized. The liposomes were physicochemically characterized (size and zeta-potential) and they were found stable at 4 degrees C over a period of 4 weeks. In vitro, liposomes 1 and 2 were about twice more active than HePC against Leishmania donovani WT whereas liposomes 3 were about three times more active than HePC on HePC-resistant promastigotes. Although liposomes 1-3 were inactive on the in vitro intramacrophage amastigote model, the ability of the liposomes to accumulate within the liver where parasites are located justifies a further in vivo evaluation. We observed that liposome 1 was twice more active than HePC against Trypanosoma brucei brucei bloodstream forms maintained in vitro. In vivo results showed that liposomal HePC seemed to be less toxic than the free drug despite the absence of significant antitrypanosomal activity. PMID:16325367
Liposomes containing drugs for treatment of vaginal infections
Željka Paveli?; Nataša Škalko-Basnet; Ivan Jalšenjak
To develop a novel vaginal delivery system, able to effectively deliver entrapped drugs during an extended period of time at the site of action, liposomes made of phosphatidylcholine were prepared by two different methods, namely the polyol dilution method and the proliposome method. Liposomes containing three commonly applied drugs in the treatment of vaginal infections: clotrimazole, metronidazole and chloramphenicol were
Liposomal Protection of Adriamycin-induced Cardiotoxicity in Mice1
Aquilur Rahman; Andrea Kessler; Newton More; Branimir Sikic; Geoffrey Rowden; Paul Woolley; Philip S. Schein
The pharmacological and therapeutic effects of Adriamycin entrapped in positively charged and negatively charged lipo somes were compared with those of free Adriamycin in mice. Liposomes were composed of phosphatidylcholine and choles terol mixed with stearyl amine (positive charge) or phosphati- dylserine (negative charge). Positive liposomes with entrapped Adriamycin effectively retarded the in vivo uptake of drug in cardiac tissue
Recent advances in liposomal nanohybrid cerasomes as promising drug nanocarriers.
Yue, Xiuli; Dai, Zhifei
Liposomes have been extensively investigated as possible carriers for diagnostic or therapeutic agents due to their unique properties. However, liposomes still have not attained their full potential as drug and gene delivery vehicles because of their insufficient morphological stability. Recently, a super-stable and freestanding hybrid liposomal cerasome (partially ceramic- or silica-coated liposome) has drawn much attention as a novel drug delivery system because its atomic layer of polyorganosiloxane surface imparts higher morphological stability than conventional liposomes and its liposomal bilayer structure reduces the overall rigidity and density greatly compared to silica nanoparticles. Cerasomes are more biocompatible than silica nanoparticles due to the incorporation of the liposomal architecture into cerasomes. Cerasomes combine the advantages of both liposomes and silica nanoparticles but overcome their disadvantages so cerasomes are ideal drug delivery systems. The present review will first highlights some of the key advances of the past decade in the technology of cerasome production and then review current biomedical applications of cerasomes, with a view to stimulating further research in this area of study. PMID:24368133
A Molecular Communication Interface Using Liposomes with Gap Junction Proteins
Yuki Moritani; Shin-ichiro M. Nomura; Satoshi Hiyama; Kazunari Akiyoshi; Tatsuya Suda
Molecular communication is an emerging communication paradigm that uses molecules as a communication medium. Molecular communication allows biological and artificially created nano- or cell-scale devices to communicate with each other. This paper proposes a molecular communication system that uses liposomes with gap junction proteins as an interface. A liposome acts as a container of information molecules, and information molecules propagate
LEE Soo Yeon Female
Liposomes, also known as nontoxic, biodegradable, and non-immunogenic therapeutic delivery vehicles, have been proposed as a carrier for drugs and antitumor agents in cancer chemotherapy. Echogenic liposomes (ELIP) have the potential to entrap air or bioactive gas to enhance acoustic reflectivity in ultrasound and are used as a contrast agent. The innovative part of this study is based on a
Structural properties of liposomes from digital holographic microscopy
NASA Astrophysics Data System (ADS)
Di Maio, Isabelle L.; Carl, Daniel; Langehanenberg, Patrik; Valenzuela, Stella M.; Battle, Andrew R.; Al Khazaaly, Sabah; Killingsworth, Murray; Kemper, Bjorn; von Bally, Gert; Martin, Donald K.
We have constructed liposomes from L alpha Phosphatidylcholine (PC) lipids, which are biomimetic lipids similar to those present in the membranes of mammalian cells. We propose an advance in the use of liposomes, such as for drug delivery, to incorporate into the liposomal membranes transport proteins that have been extracted from the lipid membranes of mammalian cells. In this paper, we describe the usage of a novel optical microscope to characterize the nanomechanical properties of these liposomes. We have applied the technique of digital holographic microscopy, using an instrument recently developed at the University of Münster, Germany. This system enabled us to measure quantitatively the structural changes in liposomes. We have investigated the deformations of these biomimetic lipids comprising these liposomes by applying osmotic stresses, in order to gain insight into the membrane environment prior to incorporation of cloned membrane transport proteins. This control of the nanomechanical properties is important in the stresses transmitted to mechanosensitive ion channels that we have incorporated into the liposomal membranes. These liposomes provide transporting vesicles that respond to mechanical stresses, such as those that occur during implantation.
Development of liposome encapsulated clindamycin for treatment of acne vulgaris
Lidija Honzak; Marjeta Šentjurc
The enhancement of topical delivery of hydrophilic substances by use of multilammelar liposomes was measured ex vivo on pig ear skin and in vivo on hairless mice by electron paramagnetic resonance method (EPR). Multilamellar liposomes with different lipid composition (final concentration of membrane components is 48 mg\\/ml) were loaded with a hydrophilic spin probe GluSL, which does not penetrate the
Galactodendritic Phthalocyanine Targets Carbohydrate-Binding Proteins Enhancing Photodynamic Therapy
Pereira, Patrícia M. R.; Silva, Sandrina; Cavaleiro, José A. S.; Ribeiro, Carlos A. F.; Tomé, Joăo P. C.; Fernandes, Rosa
Photosensitizers (PSs) are of crucial importance in the effectiveness of photodynamic therapy (PDT) for cancer. Due to their high reactive oxygen species production and strong absorption in the wavelength range between 650 and 850 nm, where tissue light penetration is rather high, phthalocyanines (Pcs) have been studied as PSs of excellence. In this work, we report the evaluation of a phthalocyanine surrounded by a carbohydrate shell of sixteen galactose units distributed in a dendritic manner (PcGal16) as a new and efficient third generation PSs for PDT against two bladder cancer cell lines, HT-1376 and UM-UC-3. Here, we define the role of galacto-dendritic units in promoting the uptake of a Pc through interaction with GLUT1 and galectin-1. The photoactivation of PcGal16 induces cell death by generating oxidative stress. Although PDT with PcGal16 induces an increase on the activity of antioxidant enzymes immediately after PDT, bladder cancer cells are unable to recover from the PDT-induced damage effects for at least 72 h after treatment. PcGal16 co-localization with galectin-1 and GLUT1 and/or generation of oxidative stress after PcGal16 photoactivation induces changes in the levels of these proteins. Knockdown of galectin-1 and GLUT1, via small interfering RNA (siRNA), in bladder cancer cells decreases intracellular uptake and phototoxicity of PcGal16. The results reported herein show PcGal16 as a promising therapeutic agent for the treatment of bladder cancer, which is the fifth most common type of cancer with the highest rate of recurrence of any cancer. PMID:24763311
Photodynamic and sonodynamic treatment by phthalocyanine on cancer cell lines.
Kolarova, Hana; Tomankova, Katerina; Bajgar, Robert; Kolar, Petr; Kubinek, Roman
Photodynamic therapy is a modality of treatment for tumors. The photochemical interactions of sensitizer, light and molecular oxygen produce reactive oxygen species (ROS) such as singlet oxygen, peroxide, hydroxyl radical and superoxide ion. The tumor is destroyed either by the formation of highly reactive singlet oxygen (type II mechanism) or by the formation of radical products (type 1 mechanism) generated in an energy transfer reaction. The resulting damage to organelles within malignant cells leads to tumor ablation. The cellular effects include membrane damage, mitochondrial damage and DNA damage. A new treatment modality called sonodynamic therapy has been developed, in which the ultrasound-induced cytotoxicity of sonochemical sensitizers inhibits tumor growth. In this study, the promising new generation of sensitizers - phthalocyanines - were used to induce the photodamage. In addition, we applied an ultrasound treatment to support the photodynamic effect. We report on the production of ROS in G361 melanoma cells. Light-emitting diodes were used to evoke the photodynamic effect. Changes in cells were evaluated using fluorescence microscope and atomic force microscopy. The quantitative ROS production changes in relation to sensitizer concentration, irradiation doses and ultrasound intensity were proved by a fluororeader. Our results showed the highest generation of ROS within G361 melanoma cells was achieved at an irradiation dose of 15 Jcm(-2) followed by ultrasound treatment at intensity of 2 Wcm(-2) and frequency of 1 MHz in the presence of 100 muM chloroaluminum phthalocyanine disulfonate (ClAlPcS2). These results suggest that ClAlPcS2 is a potential photosensitizer and sonosensitizer for sonodynamic or photodynamic treatment of cancer. PMID:19515482
Membrane fusion plays an important role in gene transfection mediated by cationic liposomes
Ari Noguchi; Tadahide Furuno; Chiyo Kawaura; Mamoru Nakanishi
By confocal laser scanning microscopy (CLSM) we have studied the membrane fusion between cationic liposomes and the endosome membranes involved in gene transfection mediated by cationic liposomes. Antisense oligonucleotides were transferred by cationic liposomes with a cationic cholesterol derivative, cholesteryl-3?-carboxyamidoethylenedimethylamine (I). Cationic liposomes were made by a mixture of the derivative I and DOPE. The intracellular distribution of fluorescein-conjugated antisense
Steric Stabilization of Liposomes by pH-Responsive N-Isopropylacrylamide Copolymer
Pezolet, Michel
polymer/liposome complexes have been developed to avoid the limitations associated with PE-based liposomes was determined in rats following the intravenous injection of 67 Ga-loaded liposomes with or without the polymer incubation in serum. In vivo, the polymer-coated liposomes exhibited a prolonged circulation time in rats
Nano or Submicron-Sized Liposomes as Carriers for Drug Delivery
Jia-You Fang
Liposomes are tiny spheres ranging in diameters from 50 nm to several microns. The scope of this mini review is to introduce the concept of liposomes and to describe some aspects and mechanisms of stimulating topical and injectable products with liposomes. Two examples discussed in this article are topical delivery across skin and injectable formulations for anticancer drugs. Classic liposomes
Surface conductivity of counter ions on protein-adsorbed lipid liposomes
Hideo Matsumura; Svetlana V Verbich; Mariana N Dimitrova
It has been reported that di-valent metal ions as compensation charges for the surface charges on liposomes have a mobility in the stagnant layer around the liposome particles. In this study, the influence of protein molecules adsorbed on the liposome surface on the mobility of counter ions around the particles is studied by the measurements of electrophoresis of liposome particles
Ligandreceptor binding on nanoparticle-stabilized liposome surfaces Liangfang Zhang,a
Granick, Steve
Ligandreceptor binding on nanoparticle-stabilized liposome surfaces Liangfang Zhang,a Kevin the access of receptor (streptavidin) to liposome- immobilized ligand (biotin) in cases where the liposomes over that range of nanoparticle surface coverage where liposome fusion and large- scale aggregation
C H A P T E R O N E Tubular Liposomes with Variable
Erickson, Harold P.
C H A P T E R O N E Tubular Liposomes with Variable Permeability for Reconstitution of FtsZ RingsZ-YFP-mts 6 5. Renatured Preparation of FtsZ-YFP-mts 7 6. Tubular Multilamellar Liposome Preparation 7 7. Permeability of the Multilamellar Liposomes 9 8. Z-ring Formation in Liposomes 11 9. A Crude Flow Chamber
pH-Dependent Fusion between the Semliki Forest Virus Membrane and Liposomes
Judy White; Ari Helenius
Semliki Forest virus was mixed with liposomes containing phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and cholesterol. When the pH of the mixture was dropped to 6 or below, rapid fusion between the membranes of the virus and the liposomes occurred, resulting in the transfer of viral nucleocapsids into the liposomes. Fusion was demonstrated biochemically by trapping RNase or trypsin within the liposomes. Trapped
In Vivo Monitoring of Tissue Pharmacokinetics of Liposome/Drug Using MRI: Illustration of Targeted
In Vivo Monitoring of Tissue Pharmacokinetics of Liposome/Drug Using MRI: Illustration of Targeted if MnSO4/doxoru- bicin (DOX) loaded liposomes could be used for in vivo moni- toring of liposome liposomes selectively but heterogeneously accumulated in the tumor region. The ther- mally sensitive
The Structure of DNA-Liposome Complexes Danilo D. Lasic,*, Helmut Strey, Mark C. A. Stuart,
Podgornik, Rudolf
The Structure of DNA-Liposome Complexes Danilo D. Lasic,*, Helmut Strey, Mark C. A. Stuart,§ Rudolf cells in ViVo seems to be the main obstacle in successful medical applications.1 Cationic liposomes were liposome kits, however, the structure of DNA-cationic liposome complexes is still not yet well understood
Use of Adaptive Focused Acoustics™ ultrasound in controlling liposome formation.
Shen, Katherine C; Kakumanu, Srikanth; Beckett, Carl D; Laugharn, James A
Many techniques for producing large unilamellar vesicles (LUVs) or small unilamellar vesicles (SUVs) have drawbacks, including exposure of sensitive biological materials to harsh organic solvents or high temperatures. Here we describe the use of controlled focused ultrasound, Adaptive Focused Acoustics™ (AFA), to make LUV or SUV at low temperature without organic solvents and at a consistent, chosen size. We studied the effects of peak incident power (PIP), cycles per burst (CPB), duty factor (DF), temperature, and lipid composition (natural or synthetic), on liposome size distribution. We found that an increase in PIP, DF, CPB, or temperature decreased liposome size. When processed under the same conditions as the natural lipid composition [Phospholipon 90 G], the synthetic lipid composition [HSPC, DSPE-PEG-2000, Chol] generally produced larger liposomes, although extending processing time reduced liposomes to similar size. In combination with AFA, these trends can help pinpoint parameter values that achieve a desired liposome size distribution. PMID:25935594
Microfabrication of three-dimensional filters for liposome extrusion
NASA Astrophysics Data System (ADS)
Baldacchini, Tommaso; Nuńez, Vicente; LaFratta, Christopher N.; Grech, Joseph S.; Vullev, Valentine I.; Zadoyan, Ruben
Liposomes play a relevant role in the biomedical field of drug delivery. The ability of these lipid vesicles to encapsulate and transport a variety of bioactive molecules has fostered their use in several therapeutic applications, from cancer treatments to the administration of drugs with antiviral activities. Size and uniformity are key parameters to take into consideration when preparing liposomes; these factors greatly influence their effectiveness in both in vitro and in vivo experiments. A popular technique employed to achieve the optimal liposome dimension (around 100 nm in diameter) and uniform size distribution is repetitive extrusion through a polycarbonate filter. We investigated two femtosecond laser direct writing techniques for the fabrication of three-dimensional filters within a microfluidics chip for liposomes extrusion. The miniaturization of the extrusion process in a microfluidic system is the first step toward a complete solution for lab-on-a-chip preparation of liposomes from vesicles self-assembly to optical characterization.
Electromagnetic field triggered drug and chemical delivery via liposomes
Liburdy, Robert P. (1820 Mountain View Rd., Tiburon, CA 94920)
The present invention relates to a system and to a method of delivering a drug to a preselected target body site of a patient, comprising the steps of encapsulating the chemical agent within liposomes, essentially temperature insensitive, i.e. not having a specific predetermined phase transition temperature within the specific temperature range of drug administration; administering the liposomes to the target body site; and subjecting the target body site to nonionizing electromagnetic fields in an area of the preselected target body in order to release said chemical agent from the liposomes at a temperature of between about +10 and 65.degree. C. The invention further relates to the use of said liposomes to bind to the surface of or to enter target tissue or an organ in a living system, and, when subjected to a nonionizing field, to release a drug from the liposomes into the target site.
Electromagnetic field triggered drug and chemical delivery via liposomes
Liburdy, R.P.
The present invention relates to a system and to a method of delivering a drug to a preselected target body site of a patient, comprising the steps of encapsulating the chemical agent within liposomes, essentially temperature insensitive, i.e. not having a specific predetermined phase transition temperature within the specific temperature range of drug administration; administering the liposomes to the target body site; and subjecting the target body site to nonionizing electromagnetic fields in an area of the preselected target body in order to release the chemical agent from the liposomes at a temperature of between about +10 and 65 C. The invention further relates to the use of the liposomes to bind to the surface of or to enter target tissue or an organ in a living system, and, when subjected to a nonionizing field, to release a drug from the liposomes into the target site.
The Treatment of Breast Cancer Using Liposome Technology
Brown, Sarah; Khan, David R.
Liposome-based chemotherapeutics used in the treatment of breast cancer can in principle enhance the therapeutic index of otherwise unencapsulated anticancer drugs. This is partially attributed to the fact that encapsulation of cytotoxic agents within liposomes allows for increased concentrations of the drug to be delivered to the tumor site. In addition, the presence of the phospholipid bilayer prevents the encapsulated active form of the drug from being broken down in the body prior to reaching tumor tissue and also serves to minimize exposure of the drug to healthy sensitive tissue. While clinically approved liposome-based chemotherapeutics such as Doxil have proven to be quite effective in the treatment of breast cancer, significant challenges remain involving poor drug transfer between the liposome and cancerous cells. In this review, we discuss the recent advancements made in the development of liposome-based chemotherapeutics with respect to improved drug transfer for use in breast cancer therapy. PMID:22506119
Shrinkage of pegylated and non-pegylated liposomes in serum.
Wolfram, Joy; Suri, Krishna; Yang, Yong; Shen, Jianliang; Celia, Christian; Fresta, Massimo; Zhao, Yuliang; Shen, Haifa; Ferrari, Mauro
An essential requisite for the design of nanodelivery systems is the ability to characterize the size, homogeneity and zeta potential of nanoparticles. Such properties can be tailored in order to create the most efficient drug delivery platforms. An important question is whether these characteristics change upon systemic injection. Here, we have studied the behavior of phosphatidylcholine/cholesterol liposomes exposed to serum proteins. The results reveal a serum-induced reduction in the size and homogeneity of both pegylated and non-pegylated liposomes, implicating the possible role of osmotic forces. In addition, changes to zeta-potential were observed upon exposing liposomes to serum. The liposomes with polyethylene glycol expressed different characteristics than their non-polymeric counterparts, suggesting the potential formation of a denser protein corona around the non-pegylated liposomes. PMID:24216620
Liposomes tethered to a biopolymer film through the hydrophobic effect create a highly effective lubricating surface.
Zheng, R; Arora, J; Boonkaew, B; Raghavan, S R; Kaplan, D L; He, J; Pesika, N S; John, V T
Liposomal coatings are formed on films of a biopolymer, hydrophobically modified chitosan (hm-chitosan), containing dodecyl groups as hydrophobes along the polymer backbone. The alkyl groups insert themselves into the liposome bilayer through hydrophobic interactions and thus tether liposomes, leading to a densely packed liposome layer on the film surface. Such liposomal surfaces exhibit effective lubrication properties due to their high degree of hydration, and reduce the coefficient of friction to the biologically-relevant range. The compliancy and robustness of these tethered liposomes allow retention on the film surface upon repeated applications of shear. Such liposome coated films have potential applications in biolubrication. PMID:25315119
Clearance and localization of intravitreal liposomes in the aphakic vitrectomized eye
Stern, W.H.; Heath, T.D.; Lewis, G.P.; Guerin, C.J.; Erickson, P.A.; Lopez, N.G.; Hong, K.L.
The authors have examined the fate of intravitreally injected liposomes in the aphakic, vitrectomized eye of the rabbit. Liposomes labelled with /sup 125/(I)-p-hydroxybenzimidylphosphatidylethanolamine were eliminated rapidly from the intraocular fluid. Nonetheless, a significant fraction of these liposomes were found to bind to various ocular tissues including the retina, iris, sclera, and cornea. Ultrastructural studies with gold colloid-loaded liposomes revealed that retinal bound liposomes were attached to the inner limiting lamina but did not penetrate to the internal cells of the retina. Epiretinal cells bound and internalized gold colloid-loaded liposomes suggesting that these cells may be very sensitive to liposome mediated drug delivery.
Simultaneous Production of Superoxide Radical and Singlet Oxygen by Sulphonated Chloroaluminum Phthalocyanine Incorporated in Human Low-density Lipoproteins: Implications for Photodynamic Therapy¶
Joana Martins; Leonor Almeida; Joăo Laranjinha
Sulfonated chloroaluminum phthalocyanines have been studied for their use in the photodynamic therapy (PDT) of tumors. Plasma low-density lipoproteins (LDL) are important carriers of phthalocyanines in the blood, but on exposure to visible light, phthalocyanine-loaded LDL undergo an oxida- tion process that propagates to erythrocytes. We attempted to identify the reactive species involved in LDL and erythrocyte oxidation by means
Electronic structure at transition metal phthalocyanine-transition metal oxide interfaces: Cobalt phthalocyanine on epitaxial MnO films
NASA Astrophysics Data System (ADS)
Glaser, Mathias; Peisert, Heiko; Adler, Hilmar; Aygül, Umut; Ivanovic, Milutin; Nagel, Peter; Merz, Michael; Schuppler, Stefan; Chassé, Thomas
The electronic structure of the interface between cobalt phthalocyanine (CoPc) and epitaxially grown manganese oxide (MnO) thin films is studied by means of photoemission (PES) and X-ray absorption spectroscopy (XAS). Our results reveal a flat-lying adsorption geometry of the molecules on the oxide surface which allows a maximal interaction between the ?-system and the substrate. A charge transfer from MnO, in particular, to the central metal atom of CoPc is observed by both PES and XAS. The change of the shape of N-K XAS spectra at the interface points, however, to the involvement of the Pc macrocycle in the charge transfer process. As a consequence of the charge transfer, energetic shifts of MnO related core levels were observed, which are discussed in terms of a Fermi level shift in the semiconducting MnO films due to interface charge redistribution.
Light induced cytosolic drug delivery from liposomes with gold nanoparticles.
Lajunen, Tatu; Viitala, Lauri; Kontturi, Leena-Stiina; Laaksonen, Timo; Liang, Huamin; Vuorimaa-Laukkanen, Elina; Viitala, Tapani; Le Guével, Xavier; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto
Externally triggered drug release at defined targets allows site- and time-controlled drug treatment regimens. We have developed liposomal drug carriers with encapsulated gold nanoparticles for triggered drug release. Light energy is converted to heat in the gold nanoparticles and released to the lipid bilayers. Localized temperature increase renders liposomal bilayers to be leaky and triggers drug release. The aim of this study was to develop a drug releasing system capable of releasing its cargo to cell cytosol upon triggering with visible and near infrared light signals. The liposomes were formulated using either heat-sensitive or heat- and pH-sensitive lipid compositions with star or rod shaped gold nanoparticles. Encapsulated fluorescent probe, calcein, was released from the liposomes after exposure to the light. In addition, the pH-sensitive formulations showed a faster drug release in acidic conditions than in neutral conditions. The liposomes were internalized into human retinal pigment epithelial cells (ARPE-19) and human umbilical vein endothelial cells (HUVECs) and did not show any cellular toxicity. The light induced cytosolic delivery of calcein from the gold nanoparticle containing liposomes was shown, whereas no cytosolic release was seen without light induction or without gold nanoparticles in the liposomes. The light activated liposome formulations showed a controlled content release to the cellular cytosol at a specific location and time. Triggering with visual and near infrared light allows good tissue penetration and safety, and the pH-sensitive liposomes may enable selective drug release in the intracellular acidic compartments (endosomes, lysosomes). Thus, light activated liposomes with gold nanoparticles are an attractive option for time- and site-specific drug delivery into the target cells. PMID:25701610
Oxidation induced by phthalocyanine dyes causes rapid calcium release from sarcoplasmic reticulum vesicles.
Abramson, J J; Cronin, J R; Salama, G
The copper containing phthalocyanine dyes, alcian blue, copper phthalocyanine tetrasulfonic acid, and Luxol fast blue MBSN are found to induce rapid calcium efflux from actively loaded sarcoplasmic reticulum (SR) vesicles. Alcian blue (5 microM), with 1 mM free Mg2+ triggered Ca2+ efflux at rates greater than 20 nmol/mg of SR/s. As in the case of Ca2+ efflux induced by calcium, heavy metals, or SH oxidation with Cu2+/cysteine, efflux induced by phthalocyanines is also stimulated by adenine containing nucleotides and inhibited by millimolar Mg2+ and submicromolar ruthenium red (RR). In addition, analogs of RR, such as hexamminecobalt(III) chloride or hexammineruthenium(III) chloride also inhibit Ca2+ efflux but are effective at somewhat higher concentrations (approximately 50 microM). Calcium release stimulated by phthalocyanines is specific for SR derived from the terminal cisternae region rather than longitudinal SR. Preincubation of alcian blue with the reducing agents, sodium dithionite, dithiothreitol, or cysteine causes complete loss of Ca2+ release activity from SR vesicles. Reoxidation of the alcian blue leads to return of the Ca2+ release activity of the phthalocyanine dye. The copper containing phthalocyanine dyes appear to cause rapid Ca2+ release from SR vesicles by oxidizing sulfhydryl groups associated with the calcium release channel. Moreover, phthalocyanines appear to act by oxidizing a pair of neighboring sulfhydryls to a disulfide because subsequent additions of the reducing agent dithiothreitol promote the closure of the Ca2+ channel and calcium re-uptake. PMID:2454077
Evaluation of systemic and mucosal immune responses following the nasal immunization by various sizes of liposomes encapsulated with tetanus toxoid
M. Tafaghodi; M. R. Jaafari; A. Nikouzadeh
Objective Liposomes have been identified as effective immunological adjuvants and have potential for the intranasal and oral delivery of protein antigens. The physicochemical properties of liposomes including the liposome size can influence their utility as a delivery system and vaccine adjuvant. Materials and Methods Following nasal administration of liposomes, the effect of various sizes of extruded liposomes encapsulated with tetanus
Analysis of individual lipoproteins and liposomes
Robbins, D.L.; Keller, R.A.; Nolan, J.P. [and others
We describe the application of single molecule detection (SMD) technologies for the analysis of natural (serum lipoproteins) and synthetic (liposomes) transport systems. The need for advanced analytical procedures of these complex and important systems is presented with the specific enhancements afforded by SMD with flowing sample streams. In contrast to bulk measurements which yield only average values, measurement of individual species allows creation of population histograms from heterogeneous samples. The data are acquired in minutes and the analysis requires relatively small sample quantities. Preliminary data are presented from the analysis of low density lipoprotein, and multilamellar and unilamellar vesicles.
Distribution of single-walled carbon nanotubes in pyrene containing liquid crystalline asymmetric zinc phthalocyanine matrix.
Tuncel, Sinem; Kaya, Esra Nur; Durmu?, Mahmut; Basova, Tamara; Gürek, Ay?e Gül; Ahsen, Vefa; Banimuslem, Hikmat; Hassan, Aseel
A novel pyrene containing asymmetric Zn(II) phthalocyanine (AB3 type) was synthesized and characterized by various spectroscopic techniques as well as elemental analysis. A symmetric polyoxyethylene substituted Zn(II) phthalocyanine (B4 type) derivative was also prepared in order to compare the properties and determine the effect of the pyrene group on the phthalocyanine molecule. Composites of synthesized zinc(II) phthalocyanine-single wall carbon nanotubes (ZnPc-SWCNTs) containing 1 and 2 wt% carbon nanotubes were prepared by mixing these two components in dichloromethane followed by removal of the solvent and drying under vacuum. The liquid crystalline properties of the pure compounds and their composites were investigated in comparison with symmetric polyoxyethylene substituted Zn(II) phthalocyanine (B4 type) by using polarized optical microscopy, differential scanning calorimetry and X-ray diffraction analysis. The distribution of the SWCNTs in the ordered matrix of the columnar mesophase of these derivatives was studied by the method of polarized Raman spectroscopy and scanning electron microscopy (SEM). It was shown that the nature of the mesophases was not altered in these composites. The I(V) dependencies for the films deposited onto interdigitated electrodes were measured and it was shown that the lateral conductivity tends to increase with increasing SWCNT concentration. PMID:24468739
Liposomes in topical ophthalmic drug delivery: an update.
Agarwal, Renu; Iezhitsa, Igor; Agarwal, Puneet; Abdul Nasir, Nurul Alimah; Razali, Norhafiza; Alyautdin, Renad; Ismail, Nafeeza Mohd
Abstract Topical route of administration is the most commonly used method for the treatment of ophthalmic diseases. However, presence of several layers of permeation barriers starting from the tear film till the inner layers of cornea make it difficult to achieve the therapeutic concentrations in the target tissue within the eye. In order to circumvent these barriers and to provide sustained and targeted drug delivery, tremendous advances have been made in developing efficient and safe drug delivery systems. Liposomes due to their unique structure prove to be extremely beneficial drug carriers as they can entrap both the hydrophilic and hydrophobic drugs. The conventional liposomes had several drawbacks particularly their tendency to aggregate, the instability and leakage of entrapped drug and susceptibility to phagocytosis. Due to this reason, for a long time, liposomes as drug delivery systems did not attract much attention of researchers and clinicians. However, over recent years development of new generation liposomes has opened up new approaches for targeted and sustained drug delivery using liposomes and has rejuvenated the interest of researchers in this field. In this review we present a summary of current literature to understand the anatomical and physiological limitation in achieving adequate ocular bioavailability of topically applied drugs and utility of liposomes in overcoming these limitations. The recent developments related to new generation liposomes are discussed. PMID:25116511
Sterically stabilized liposomes as a potent carrier for shikonin.
Kontogiannopoulos, K N; Tsermentseli, S K; Assimopoulou, A N; Papageorgiou, V P
The ability of pegylated liposomes (sterically stabilized liposomes-SSL) to localize in solid tumors via the enhanced permeability and retention (EPR) effect, partly depends on their long circulating properties which can be achieved by grafting polyethylene glycol (PEG) to the liposomes' surface. Alkannin and shikonin (A/S) are naturally occurring hydroxynaphthoquinones with a well-established spectrum of wound healing, antimicrobial, anti-inflammatory, antioxidant, and recently established antitumor activity. The purpose of this work was to prepare and characterize shikonin-loaded pegylated liposomes as a new drug carrier for shikonin, as a continuation of authors' previous work on conventional shikonin-loaded liposomal formulations. Three new pegylated liposomal formulations of shikonin (DSPC-PEG2000, EPC-PEG2000, and DPPC-PEG2000) were prepared and characterized in terms of physicochemical characteristics, pharmacokinetics, and stability (at 4?°C, for 28?d) and compared with the corresponding conventional ones. Particle size distribution, ?-potential, entrapment efficiency, and release profile of the entrapped drug were measured. Results indicated the successful incorporation of shikonin into liposomes alongside with their good physicochemical characteristics, high entrapment efficiency, satisfactory in vitro release profile, and good physical stability. The results are considered promising and could be used as a road map for designing further in vivo experiments. PMID:24597496
Modulation of the carotenoid bioaccessibility through liposomal encapsulation.
Tan, Chen; Zhang, Yating; Abbas, Shabbar; Feng, Biao; Zhang, Xiaoming; Xia, Shuqin
The low bioaccessibility of carotenoids is currently a challenge to their incorporation in pharmaceutics, nutraceuticals and functional foods. The aim of this study was to evaluate the modulating effects of liposome encapsulation on the bioaccessibility, and its relationship with carotenoid structure and incorporated concentration. The physical stability of liposomes, lipid digestibility, carotenoids release and bioaccessibility were investigated during incubation in a simulated gastrointestinal tract. Analysis on the liposome size and morphology showed that after digestion, the majority of particles maintained spherical shape with only an increase of size in liposomes loading ?-carotene or lutein. However, a large proportion of heterogeneous particles were visible in the micelle phase of liposomes loading lycopene or canthaxanthin. It was also found that the release of lutein and ?-carotene from liposomes was inhibited in a simulated gastric fluid, while was slow and sustained in a simulated intestinal fluid. By contrast, lycopene and canthaxanthin exhibited fast and considerable release in the gastrointestinal media. Both carotenoid bioaccessibility and micellization content decreased with the increase of incorporated concentration. Anyway, the bioaccessibility of carotenoids after encapsulated in liposomes was in the following order: lutein>?-carotene>lycopene>canthaxanthin. Bivariate correlation analysis revealed that carotenoid bioaccessibility depended strongly on the incorporating ability of carotenoids into a lipid bilayer, loading content, and nature of the system. PMID:25456993
Liposome formation with wool lipid extracts rich in ceramides.
Ramírez, R; Martí, M; Cavaco-Paulo, A; Silva, R; de la Maza, A; Parra, J L; Coderch, L
Internal wool lipids (IWLs) are rich in cholesterol, free fatty acids, cholesteryl sulfate, and, mainly, ceramides. The repairing effect of these lipids structured as liposomes was demonstrated by reinforcing the skin-barrier integrity and increasing the water-holding capacity when applied onto the skin. This work was focused on the formation of liposomes with IWLs rich in ceramides, obtained at pilot plant level with organic solvent extraction by using methanol and acetone. The lipid composition of the two extracts was quantitatively analyzed. IWL extracts containing different amounts of sterol sulfate were used to form liposomes at physiologic p(H). Vesicle size distribution, polydispersity index, and zeta potential of all liposomes were determined to characterize them and to study their stability. The results obtained showed that IWL extract composition, which was different depending on the extraction methodologies used, greatly influences the characteristics of the liposomes formed. Vesicular size and polydispersity index liposomes were smaller when the extract composition contained a higher proportion of either free fatty acids or sterol sulfate. Moreover, liposome stability was improved when some amount of sterol sulfate was added to the composition of methanol and acetone extracts. This natural mixture with keratinaceous origin could have a special interest for cosmetic or dermopharmaceutical companies. PMID:19515010
Enhanced in vivo bioluminescence imaging using liposomal luciferin delivery system
Kheirolomoom, Azadeh; Kruse, Dustin E.; Qin, Shengping; Watson, Katherine E.; Lai, Chun-Yen; Young, Lawrence J.T.; Cardiff, Robert D.; Ferrara, Katherine W.
To provide a continuous and prolonged delivery of the substrate D-luciferin for bioluminescence imaging in vivo, luciferin was encapsulated into liposomes using either the pH-gradient or acetate-gradient method. Under optimum loading conditions, 0.17 mg luciferin was loaded per mg of lipid with 90–95% encapsulation efficiency, where active loading was 6 to 18-fold higher than obtained with passive loading. Liposomal luciferin in a long-circulating formulation had good shelf stability, with 10% release over 3-month storage at 4°C. Pharmacokinetic profiles of free and liposomal luciferin were then evaluated in transgenic mice expressing luciferase. In contrast to rapid in vivo clearance of free luciferin (t1/2=3.54 min), luciferin encapsulated into long-circulating liposomes showed a prolonged release over 24 hours. The first order release rate constant of luciferin from long-circulating liposomes, as estimated from the best fit of the analytical model to the experimental data, was 0.01 h?1. Insonation of luciferin-loaded temperature sensitive liposomes directly injected into one tumor of Met1-luc tumor-bearing mice resulted in immediate emission of light. Systemic injection of luciferin-loaded long-circulating liposomes into Met1-luc tumor-bearing mice, followed by unilateral ultrasound-induced hyperthermia, produced a gradual increase in radiance over time, reaching a peak 4–7 h post-ultrasound. PMID:19748536
Development of liposomal salbutamol sulfate dry powder inhaler formulation.
Huang, Wen-Hua; Yang, Zhi-Jun; Wu, Heng; Wong, Yuen-Fan; Zhao, Zhong-Zhen; Liu, Liang
The purpose of our study was to develop a formulation of liposomal salbutamol sulfate (SBS) dry powder inhaler (DPI) for the treatment of asthma. Liposomes of high encapsulation efficiency (more than 80%) were prepared by a vesicular phospholipid gel (VPG) technique. SBS VPG liposomes were subjected to lyophilization using different kinds of cryoprotectants in various mass ratios. Coarse lactose (63-106 microm) in different mass ratios was used as a carrier. Magnesium stearate (0.5%) was added as a lubricator. The dry liposomal powders were then crushed by ball milling and sieved through a 400-mesh sieve to control the mean particle size at about 10 microm. The effects of different kinds of cryoprotectants and the amount of lactose carrier on the fine particle fraction (FPF) of SBS were investigated. The results showed that the developed formulation of liposomal dry powder inhaler was obtained using lactose as a cryoprotectant with a mass ratio of lyophilized powder to carrier lactose at 1 : 5; 0.5% magnesium stearate was used as a lubricator. The value of FPF for SBS was 41.51+/-2.22% for this formulation. Sustained release of SBS from the VPG liposomes was found in the in vitro release study. The study results offer the promising possibility of localized pulmonary liposomal SBS delivery in the anhydrous state. PMID:20190418
Formation of bovine serum albumin associates with zinc tetra(4,4'-carboxy)phenylamino- and tetra-(4,4'-carboxy)phenoxy phthalocyanines in aqueous-organic solutions at 298 K
NASA Astrophysics Data System (ADS)
Lebedeva, N. Sh.; Popova, T. E.; Mal'kova, E. A.; Gubarev, Yu. A.
The states of water-soluble complexes of zinc phthalocyanine containing -O-C6H4-COONa and -NH-C6H4-COONa substituents in aqueous and organic media are studied. The type of dimerization is determined for each phthalocyanine. Phthalocyanine interaction with bovine serum albumin is studied with respect to the association equilibria. It is shown that phthalocyanines are localized in protein subdomains IB and IIA, and the interaction between protein and phthalocyanines is of a multicenter character.
Synthesis of phthalocyanine doped sol-gel materials
NASA Technical Reports Server (NTRS)
Dunn, Bruce
The synthesis of sol-gel silica materials doped with three different types of metallophthalocyanines has been studied. Homogeneous materials of good optical quality were prepared and the first optical limiting measurements of dyes in sol-gel hosts were carried out. The properties of these solid state limiters are similar to limiters based on phthalocyanine (Pc) in solution. Sol-gel silica materials containing copper, tin and germanium phthalocyanines were investigated. The initial step in all cases was to prepare silica sols by the sonogel method using tetramethoxy silane (TMOS), HCl and distilled water. Thereafter, the synthesis depended upon the specific Pc and its solubility characteristics. Copper phthalocyanine tetrasulfonic acid tetra sodium salt (CuPc4S) is soluble in water and various doping levels (1 x 10 (exp -4) M to 1 x 10 (exp -5) M) were added to the sol. The group IV Pc's, SnPc(OSi(n-hexyl)3)2 and GePc(OSi(n-hexyl)3)2, are insoluble in water and the process was changed accordingly. In these cases, the compounds were dissolved in THF and then added to the sol. The Pc concentration in the sol was 2 x 10(exp -5)M. The samples were then aged and dried in the standard method of making xerogel monoliths. Comparative nanosecond optical limiting experiments were performed on silica xerogels that were doped with the different metallophthalocyanines. The ratio of the net excited state absorption cross section (sigma(sub e)) to the ground state cross section (sigma(sub g)) is an important figure of merit that is used to characterize these materials. By this standard the SnPc sample exhibits the best limiting for the Pc doped sol-gel materials. Its cross section ratio of 19 compares favorably with the value of 22 that was measured in toluene. The GePc materials appear to not be as useful as those containing SnPc. The GePc doped solids exhibit a higher onset energy (2.5 mj and lower cross section ratio, 7. The CuPc4S sol-gel material has a still lower cross section ratio, 4, however, the tetrasulfonate groups make the dye soluble in water which greatly facilitates its incorporation into the sol-gel matrix. The nonlinear transmission of CuPc4S in a pH 2 buffer solution and in a silica xerogel were compared. It is evident that the CuPc4S preserves its optical limiting behavior in the sol-gel matrix, indicating that the fundamental excited state absorption process is essentially the same for a molecule in solution or in the solid state. Although the spectroscopic details of energy level lifetimes are unknown, the significance is that passive optical limiting has been achieved in the solid state via incorporation of a dye into an inorganic host. The only compromise occurs at the extremely high energy regime where photobleaching is observed. This is a result of the limited mobility of the dye molecules in the solid silica host relative to a liquid host. The effects of photodegradation in the xerogel are additive, whereas the solution provides a supply of fresh molecules that are free to enter the active volume between pulses.
Giant liposome preparation for imaging and patch-clamp electrophysiology.
Collins, Marcus D; Gordon, Sharona E
The reconstitution of ion channels into chemically defined lipid membranes for electrophysiological recording has been a powerful technique to identify and explore the function of these important proteins. However, classical preparations, such as planar bilayers, limit the manipulations and experiments that can be performed on the reconstituted channel and its membrane environment. The more cell-like structure of giant liposomes permits traditional patch-clamp experiments without sacrificing control of the lipid environment. Electroformation is an efficient mean to produce giant liposomes >10 ?m in diameter which relies on the application of alternating voltage to a thin, ordered lipid film deposited on an electrode surface. However, since the classical protocol calls for the lipids to be deposited from organic solvents, it is not compatible with less robust membrane proteins like ion channels and must be modified. Recently, protocols have been developed to electroform giant liposomes from partially dehydrated small liposomes, which we have adapted to protein-containing liposomes in our laboratory. We present here the background, equipment, techniques, and pitfalls of electroformation of giant liposomes from small liposome dispersions. We begin with the classic protocol, which should be mastered first before attempting the more challenging protocols that follow. We demonstrate the process of controlled partial dehydration of small liposomes using vapor equilibrium with saturated salt solutions. Finally, we demonstrate the process of electroformation itself. We will describe simple, inexpensive equipment that can be made in-house to produce high-quality liposomes, and describe visual inspection of the preparation at each stage to ensure the best results. PMID:23851612
Giant Liposome Preparation for Imaging and Patch-Clamp Electrophysiology
Collins, Marcus D.; Gordon, Sharona E.
The reconstitution of ion channels into chemically defined lipid membranes for electrophysiological recording has been a powerful technique to identify and explore the function of these important proteins. However, classical preparations, such as planar bilayers, limit the manipulations and experiments that can be performed on the reconstituted channel and its membrane environment. The more cell-like structure of giant liposomes permits traditional patch-clamp experiments without sacrificing control of the lipid environment. Electroformation is an efficient mean to produce giant liposomes >10 ?m in diameter which relies on the application of alternating voltage to a thin, ordered lipid film deposited on an electrode surface. However, since the classical protocol calls for the lipids to be deposited from organic solvents, it is not compatible with less robust membrane proteins like ion channels and must be modified. Recently, protocols have been developed to electroform giant liposomes from partially dehydrated small liposomes, which we have adapted to protein-containing liposomes in our laboratory. We present here the background, equipment, techniques, and pitfalls of electroformation of giant liposomes from small liposome dispersions. We begin with the classic protocol, which should be mastered first before attempting the more challenging protocols that follow. We demonstrate the process of controlled partial dehydration of small liposomes using vapor equilibrium with saturated salt solutions. Finally, we demonstrate the process of electroformation itself. We will describe simple, inexpensive equipment that can be made in-house to produce high-quality liposomes, and describe visual inspection of the preparation at each stage to ensure the best results. PMID:23851612
Liposomalization of SN-38 as active metabolite of CPT-11.
Sadzuka, Yasuyuki; Takabe, Hiroyuki; Sonobe, Takashi
Although many drugs have been developed for the treatment of disease, some drugs have complications such as adverse effects, and antitumor agents should target tumors or cells more selectively. It is therefore necessary to develop drug delivery systems, and liposomes are reportedly useful as an effective drug carrier. An antitumor agent, CPT-11, inhibits DNA synthesis by the inhibition of topoisomerase1 and has a strong antitumor activity. SN-38 is converted from CPT-11 as an active metabolite by carboxylesterase in the liver. As SN-38 is insoluble, it has not been applied at the clinical stage as an injection. It is expected that SN-38 liposomalization may increase its usefulness in cancer chemotherapy. Our purpose is to have a clinical application of SN-38 by a novel method of liposomalization to expand the application for the other insolubility drugs. As SN-38 is hydrophobic, SN-38-trapped liposome preparation was attempted using the Bangham method, which is effective for general preparation. However, a high ratio of SN-38 trapped in liposome was not achieved, and this was not improved by the freezing-thawing method or the freeze-drying method. On the other hand, the ratio of SN-38 trapped in liposome by the modified remote loading method was about 4 times that by the Bangham method, and the ratio by the film loading method, novel method of liposomal preparation, reached 2 times and 8 times that by the modified remote loading method and Bangham method, respectively, showing a remarkable increase. In conclusion, it was suggested that the preparation of SN-38 liposome using the film loading method effectively entraps SN-38. Thus, it is expected that SN-38 liposome can be applied as an injection. This preparation method is useful if application is possible in the other insolubility drugs. PMID:16182400
Improved stability of liposome in oil\\/water emulsion by association of amphiphilic polymer with liposome and its effect on bioactive skin permeation
Eun Chul Cho; Hyung Jun Lim; Jongwon Shim; Junoh Kim; Ih-Seop Chang
In this study, we demonstrated that the stability of phosphatidylcholine (PC)-cholesterol (Chol) liposomes can be improved in oil in water (o\\/w) emulsion by association of amphiphilic polyelectrolyte, poly(methacrylic acid-co-stearyl methacrylate) with PC–Chol liposomes. Differential scanning calorimetry and photocorrelation spectroscopy results showed that the polymer-associated liposomes were more stable than the PC–Chol liposomes when mixed with the o\\/w emulsion. This difference
Synthesis of conjugated helical polymers, cyclophanes, metal complexes and phthalocyanines
NASA Astrophysics Data System (ADS)
Fox, Joseph Michael
Pd(0) catalyzed reactions of 2,15-diethynyl (6) helicene with derivatives of p- and o-diiodobenzene give, respectively, polymers and cyclophanes, in which helicenes are linked by diethynylbenzenes. The molar rotation of polymer is greater than that of a monomeric analogue, and peaks in its UV and CD spectra at wavelengths greater than 350 nm are shifted to the red of the monomer. A cyclophane which contains two helicene rings could be isolated in pure form. (7) Helicenebisquinones can be made easily and in quantity by reacting the silyl enol ethers of a 9,10-dialkoxy-, or a 9,10-disiloxy-, 3,6-diacetylphenanthrene with p-benzoquinone. If an ethyl enol ether is used, the transformation proceeds in much lower yield. The (7) helicenes are efficiently resolved into their enantiomers, and absolute configurations are assigned. The synthesis of molecules that have copper and nickel phthalocyanine cores fused to four non-racemic (7) helicenes, is described. CD and UV-vis absorption spectroscopy show that these compounds aggregate in 75% EtOH in CHClsb3. The UV-vis absorption spectra of films of the nickel phthalocyanine are similar to those of solutions of the aggregated molecules, suggesting that the aggregates have similar structures in the neat samples and in solution. A calculation shows that the energy is minimized when the molecules stack in a chiral superstructure with a core to core distance of ca 3.4 A. Atomic Force Microscopy shows that on mica the molecules assemble into isolated stacks in which the axis of stacking is perpendicular to the surface of the substrate. Combining 1,2-phenylenediamine with a nonracemic (6) helicene-bisquinone and heating the resulting product in acetic acid gives an (8) helicene. The structure of the (8) helicene in solution is shown to be that of a vinylogous lactam. Methods are described that transform it into an (8) helicenebis-o-quinone, and this, in turn, into a helical ligand.
In vivo and in vitro evaluation of octyl methoxycinnamate liposomes
Varjăo Mota, Aline de Carvalho; Faria de Freitas, Zaida Maria; Júnior, Eduardo Ricci; Dellamora-Ortiz, Gisela Maria; Santos-Oliveira, Ralph; Ozzetti, Rafael Antonio; Vergnanini, André Luiz; Ribeiro, Vanessa Lira; Silva, Ronald Santos; dos Santos, Elisabete Pereira
Solar radiation causes damage to human skin, and photoprotection is the main way to prevent these harmful effects. The development of sunscreen formulations containing nanosystems is of great interest in the pharmaceutical and cosmetic industries because of the many potential benefits. This study aimed to develop and evaluate an octyl methoxycinnamate (OMC) liposomal nanosystem (liposome/OMC) to obtain a sunscreen formulation with improved safety and efficacy by retaining OMC for longer on the stratum corneum. Methods The liposome/OMC nanostructure obtained was tested for enzymatic hydrolysis with lipase from Rhizomucor miehei and biodistribution with liposomes labeled with technetium-99m. The liposome/OMC formulation was then incorporated in a gel formulation and tested for ocular irritation using the hen's egg test-chorio-allantoic membrane (HET-CAM) assay, in vitro and in vivo sun protection factor, in vitro release profile, skin biometrics, and in vivo tape stripping. Results The liposome/OMC nanosystem was not hydrolyzed from R. miehei by lipase. In the biodistribution assay, the liposome/OMC formulation labeled with technetium-99m had mainly deposited in the skin, while for OMC the main organ was the liver, showing that the liposome had higher affinity for the skin than OMC. The liposome/OMC formulation was classified as nonirritating in the HET-CAM test, indicating good histocompatibility. The formulation containing liposome/OMC had a higher in vivo solar photoprotection factor, but did not show increased water resistance. Inclusion in liposomes was able to slow down the release of OMC from the formulation, with a lower steady-state flux (3.9 ± 0.33 ?g/cm2/hour) compared with the conventional formulation (6.3 ± 1.21 ?g/cm2/hour). The stripping method showed increased uptake of OMC in the stratum corneum, giving an amount of 22.64 ± 7.55 ?g/cm2 of OMC, which was higher than the amount found for the conventional formulation (14.57 ± 2.30 ?g/cm2). Conclusion These results indicate that liposomes are superior carriers for OMC, and confer greater safety and efficacy to sunscreen formulations. PMID:24376350
Liposomal Drug Products: A Quality by Design Approach
NASA Astrophysics Data System (ADS)
Xu, Xiaoming
Quality by Design (QbD) principles has been applied to the development of two liposomal formulations, containing a hydrophilic small molecule therapeutic (Tenofovir) and a protein therapeutic (superoxide dismutase). The goal of the research is to provide critical information on 1) how to reduce the preparation variability in liposome formulations, and 2) how to increase drug encapsulation inside liposomes to reduce manufacturing cost. Most notably, an improved liposome preparation method was developed which increased the encapsulation efficiency of hydrophilic molecules. In particular, this method allows for very high encapsulation efficiency. For example, encapsulation efficiencies of up to 50% have been achieved, whereas previously only 20% or less have been reported. Another significant outcome from this research is a first principle mathematical model to predict the encapsulation efficiency of hydrophilic drugs in unilamellar liposomes. This mathematical model will be useful in: formulation development to rapidly achieve optimized formulations; comparison of drug encapsulation efficiencies of liposomes prepared using different methods; and assisting in the development of suitable process analytical technologies to achieve real-time monitoring and control of drug encapsulation during manufacturing. A novel two-stage reverse dialysis in vitro release testing method has also been developed for passively targeted liposomes, which uses the first stage to mimic the circulation of liposomes in the body and the second stage to imitate the drug release process at the target. The developed in vitro release testing method can be used to distinguish formulations with varied compositions for quality control testing purposes. This developed method may pave the way to the development of more biorelevant quality control testing methods for liposomal drug products in the future. The QbD case studies performed in this research are examples of how this approach can be used to obtain design space for liposome products to achieve the desired in vivo product performance criteria. From an industrial perspective, this study provides an in-depth understanding of the parameters (risks) involved in liposome formulation and processing. From a regulatory perspective, the development of QbD principles for liposomal drug products will facilitate their regulation assuring safety and efficacy of these complex delivery systems.
Application of liposomes in medicine and drug delivery.
Daraee, Hadis; Etemadi, Ali; Kouhi, Mohammad; Alimirzalu, Samira; Akbarzadeh, Abolfazl
Liposomes provide an established basis for the sustainable development of different commercial products for treatment of medical diseases by the smart delivery of drugs. The industrial applications include the use of liposomes as drug delivery vehicles in medicine, adjuvants in vaccination, signal enhancers/carriers in medical diagnostics and analytical biochemistry, solubilizers for various ingredients as well as support matrices for various ingredients and penetration enhancers in cosmetics. In this review, we summarize the main applications and liposome-based commercial products that are currently used in the medical field. PMID:25222036
Studies on precellular evolution - The encapsulation of polyribonucleotides by liposomes
NASA Technical Reports Server (NTRS)
Baeza, I.; Ibanez, M.; Santiago, J. C.; Wong, C.; Lazcano, A.
Liposomes have been suggested as possible models of precellular systems formed in the early Archean earth from lipids of nonenzymatic origin. Since it is generally accepted that RNA molecules preceded double-stranded DNA molecules as genetic material, the encapsulation of polyribonucleotides within liposomes (made from dipalmitoyl phosphatidylcholine and from egg yolk phosphatidylcholine) was studied. Quantitative determinations show that approximately 50 percent of the available lipids form liposomes, and that up to 5 percent of the polyribonucleotides can be entrapped by them. Also studied was the encapsulation of polyribonucleotides in the presence of urea and cyanamide and of Zn(2+) and Pb(2+).
External beam radiotherapy synergizes 188Re-liposome against human esophageal cancer xenograft and modulates 188Re-liposome pharmacokinetics
Chang, Chih-Hsien; Liu, Shin-Yi; Chi, Chih-Wen; Yu, Hsiang-Lin; Chang, Tsui-Jung; Tsai, Tung-Hu; Lee, Te-Wei; Chen, Yu-Jen
External beam radiotherapy (EBRT) treats gross tumors and local microscopic diseases. Radionuclide therapy by radioisotopes can eradicate tumors systemically. Rhenium 188 (188Re)-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy, with biodistribution profiles preferential to tumors. We designed a combinatory treatment and examined its effects on human esophageal cancer xenografts, a malignancy with potential treatment resistance and poor prognosis. Human esophageal cancer cell lines BE-3 (adenocarcinoma) and CE81T/VGH (squamous cell carcinoma) were implanted and compared. The radiochemical purity of 188Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT showed that BE-3, but not CE81T/VGH, xenografts could uptake the 188Re-liposome. The combination of EBRT and 188Re-liposome inhibited tumor regrowth greater than each treatment alone, as the tumor growth inhibition rate was 30% with EBRT, 25% with 188Re-liposome, and 53% with the combination treatment at 21 days postinjection. Combinatory treatment had no additive adverse effects and significant biological toxicities on white blood cell counts, body weight, or liver and renal functions. EBRT significantly enhanced the excretion of 188Re-liposome into feces and urine. In conclusion, the combination of EBRT with 188Re-liposome might be a potential treatment modality for esophageal cancer.
External beam radiotherapy synergizes (188)Re-liposome against human esophageal cancer xenograft and modulates (188)Re-liposome pharmacokinetics.
Chang, Chih-Hsien; Liu, Shin-Yi; Chi, Chih-Wen; Yu, Hsiang-Lin; Chang, Tsui-Jung; Tsai, Tung-Hu; Lee, Te-Wei; Chen, Yu-Jen
External beam radiotherapy (EBRT) treats gross tumors and local microscopic diseases. Radionuclide therapy by radioisotopes can eradicate tumors systemically. Rhenium 188 ((188)Re)-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy, with biodistribution profiles preferential to tumors. We designed a combinatory treatment and examined its effects on human esophageal cancer xenografts, a malignancy with potential treatment resistance and poor prognosis. Human esophageal cancer cell lines BE-3 (adenocarcinoma) and CE81T/VGH (squamous cell carcinoma) were implanted and compared. The radiochemical purity of (188)Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT showed that BE-3, but not CE81T/VGH, xenografts could uptake the (188)Re-liposome. The combination of EBRT and (188)Re-liposome inhibited tumor regrowth greater than each treatment alone, as the tumor growth inhibition rate was 30% with EBRT, 25% with (188)Re-liposome, and 53% with the combination treatment at 21 days postinjection. Combinatory treatment had no additive adverse effects and significant biological toxicities on white blood cell counts, body weight, or liver and renal functions. EBRT significantly enhanced the excretion of (188)Re-liposome into feces and urine. In conclusion, the combination of EBRT with (188)Re-liposome might be a potential treatment modality for esophageal cancer. PMID:26056445
Effect of sulfonation on photodynamic inactivation of living cells by aluminum phthalocyanines
NASA Astrophysics Data System (ADS)
Poroshina, Marina Y.; Chernyaeva, Elena B.; Greve, Jan; Van Leeuwen, A. G.; Puppels, Gerwin J.
During the last decade a new modality of cancer treatment appeared, called photodynamic therapy (PDT). This treatment is based on the following observation. Some dyes, administered intravenously, are preferentially retained in solid tumors as a result of as yet incompletely understood properties of malignant tissue. Subsequent exposure to light of a wavelength that is absorbed by the dye initiates a chain of events that ends in tumor necrosis. Recent results have demonstrated the considerable potential of phthalocyanines. The sulfonated derivatives of phthalocyanine metal complexes (MeSnPc) have been proposed for the photodynamic therapy since they demonstrate good efficiency of phototoxicity, are water-soluble and have a low level of dark toxicity. It was already reported that the sulfonation degree influences the photodynamic activity of MeSnPc3. The present work was undertaken to investigate some parameters that determine the photodynamic effect for aluminum phthalocyanines with different degree of sulfonation.
Highly ordered phthalocyanine thin films on a technically relevant polymer substrate
NASA Astrophysics Data System (ADS)
Peisert, H.; Liu, X.; Olligs, D.; Petr, A.; Dunsch, L.; Schmidt, T.; Chassé, T.; Knupfer, M.
We have studied the molecular orientation of well-known representatives of organic semiconductors from the family of the phthalocyanines [copper phthalocyanine (CuPc) and its perfluorinated relative (CuPcF16)] on a conducting polymer thin film using polarization-dependent x-ray absorption spectroscopy. As a polymer substrate PEDOT:PSS [a mixture of poly-3,4-ethylenedioxy-thiophene (PEDOT) and polystyrenesulfonate (PSS), which is often applied as an electrode material in (all-)organic semiconductor devices] was spin coated onto indium-tin-oxide substrates. Even if the interfaces themselves are relatively ill defined (we found recently a mixing of the two organic materials and charge-transfer processes), a very high degree of molecular ordering is observed in the 20-50nm thick phthalocyanine films.
Folate receptor mediated targeted delivery of ricin entrapped into sterically stabilized liposomes to human epidermoid carcinoma (KB) cells: effect of monensin intercalated into folate-tagged liposomes.
Tyagi, Nikhil; Ghosh, Prahlad C
Ricin was encapsulated into various sterically stabilized liposomes having different density of folate on the surface and the cytotoxicity of ricin in these liposomes was examined in KB cells. The effect of monensin in free and various sterically stabilized liposomal forms having different density of folate on the surface on the enhancement of cytotoxicity of ricin entrapped in these liposomes was also examined. It was observed that liposomal ricin having 0.5 mol% folate-PEG on the surface exhibits maximum cytotoxicity (IC(50)=1274 ng/ml) in KB cells as compared to non-targeted liposomes (IC(50)=3274 ng/ml). Monensin either in free form (266.2-fold) or liposomal form (291.5-fold) enhances the cytotoxicity of this targeted liposomal ricin significantly. This enhancement of the cytotoxicity of ricin entrapped in folate-targeted liposomes is further enhanced to 557.7-fold by monensin when it was delivered through folate-targeted (0.5 mol% folate-PEG) liposomes. The present study has clearly demonstrated that ricin entrapped in folate-tagged-sterically stabilized liposomes in combination with monensin intercalated in folate-tagged-sterically stabilized liposomes may have potential application for the treatment of cancer cells over-expressing folate receptors on the cell surface. PMID:21621613
Characterization of fatty acid liposome coated with low-molecular-weight chitosan.
Tan, Hsiao Wei; Misran, Misni
Preparation of chitosan-coated fatty acid liposomes is often restricted by the solubility of chitosan under basic conditions. In this experiment, the preparation of chitosan-coated oleic acid (OA) liposomes using low molecular weight (LMW) chitosan (10 and 25 kDA) was demonstrated. These selected LMW chitosans are water soluble. The coating of the chitosan layer on OA liposomes was confirmed by its microscope images and physicochemical properties, such as zeta potential and the size of the liposomes. The "peeling off" effect on the surface of chitosan-coated OA liposomes was observed in the atomic force microscope images and showed the occurrence of the chitosan layer on the surface of OA liposomes. The size of the chitosan-coated liposomes was at least 20?nm smaller than the OA liposomes, and the increase of zeta potential with the increasing amount of LMW chitosan further confirmed the presence of the surface modification of OA liposomes. PMID:22881198
Liposomes for targeting hepatocellular carcinoma: use of conjugated arabinogalactan as targeting ligand.
Shah, Sanket M; Goel, Peeyush N; Jain, Ankitkumar S; Pathak, Pankaj O; Padhye, Sameer G; Govindarajan, Srinath; Ghosh, Sandipto S; Chaudhari, Pradip R; Gude, Rajiv P; Gopal, Vijaya; Nagarsenker, Mangal S
Present study investigates the potential of chemically modified (Shah et al., 2013) palmitoylated arabinogalactan (PAG) in guiding liposomal delivery system and targeting asialoglycoprotein receptors (ASGPR) which are expressed in hepatocellular carcinoma (HCC). PAG was incorporated in liposomes during preparation and doxorubicin hydrochloride was actively loaded in preformed liposomes with and without PAG. The liposomal systems with or without PAG were evaluated for in vitro release, in vitro cytotoxicity, in vitro cell uptake on ASGPR(+) cells, in vivo pharmacokinetic study, in vivo biodistribution study, and in vivo efficacy study in immunocompromised mice. The particle size for all the liposomal systems was below 200 nm with a negative zeta potential. Doxorubicin loaded PAG liposomes released significantly higher amount of doxorubicin at pH 5.5 as compared to pH 7.4, providing advantage for targeted tumor therapy. Doxorubicin in PAG liposomes showed superior cytotoxicity on ASGPR(+) HepG2 cells as compared to ASGPR(-), MCF7, A549, and HT29 cells. Superior uptake of doxorubicin loaded PAG liposomes as compared to doxorubicin loaded conventional liposomes was evident in confocal microscopy studies. Higher AUC in pharmacokinetic study and higher deposition in liver was observed for PAG liposomes compared to conventional liposomes. Significantly higher tumor suppression was noted in immunocompromised mice for mice treated with PAG liposomes as compared to the conventional liposomes. Targeting ability and superior activity of PAG liposomes is established pre-clinically suggesting potential of targeted delivery system for improved treatment of HCC. PMID:25311181
Nano-liposomes of entrapment lidocaine hydrochloride on in vitro permeability of narcotic.
Sun, Nenghong; Zhu, Yanyan; Yuan, Lei; Lang, Bao
In order to explore two kinds of nano-liposomes in lidocaine hydrochloride nano-liposomes on in vitro permeability of drug, and conduct comparison and analysis, this paper investigates cumulative infiltration situation of lidocaine hydrochloride flexible nano-liposomes and ordinary nano-liposomes by using modified Franz diffusion pool on mice vitro skin. Cumulative osmotic quantity of lidocaine hydrochloride flexible nano-liposomes for 9h was higher than ordinary nano-liposomes. (t)max(Maximum osmotic quantity time) of lidocaine hydrochloride flexible nano-liposomes and ordinary nano-liposomes in mice skin was 5 and 60min, the former (C)max (maximum dosage time) was 1.2 times of the latter. Drug was not found in mice plasma of ordinary nano-liposomes group, traces of drugs was detected in 0.5 and 1h in flexible nano-liposomes group, but the concentration was lower than the effective concentration. Compared with the classic skin transparent promoter and ordinary liposome, flexible nano-liposomes have more advantages, but its stability is less than ordinary nano-liposomes because of the addition of surface active substance. Flexible nano-liposomes have great development potential as a carrier of transdermal drug delivery field. PMID:25631510
Structural analysis of ``flexible'' liposome formulations: new insights into the skin-penetrating ability of soft nanostructures
Raghavan, Srinivasa
Structural analysis of ``flexible'' liposome formulations: new insights into the skin. The main examples of these are the so-called ``flexible liposomes'', which are mixtures of lipids corneum. Here, we reexamine the structure of ``flexible'' liposome formulations and show
Amphiphilic zinc phthalocyanine photosensitizers: synthesis, photophysicochemical properties and in vitro studies for photodynamic therapy.
Çak?r, Dilek; Göksel, Meltem; Çak?r, Volkan; Durmu?, Mahmut; Biyiklioglu, Zekeriya; Kantekin, Halit
Peripherally and non-peripherally tetra-substituted zinc(ii) phthalocyanines bearing 2-(2-{2-[3-(dimethylamino)phenoxy]ethoxy}ethoxy)ethoxy and 2-(2-{2-[3-(diethylamino)phenoxy]ethoxy}ethoxy)ethoxy groups (, , and ) were synthesized by cyclotetramerization of the corresponding phthalonitriles (, , and ). Their quaternized ionic derivatives (, , and ) were also synthesized by the reaction of them with methyl iodide. The novel compounds were characterized by using standard spectroscopic techniques such as FT-IR, (1)H NMR, (13)C NMR, UV-vis, mass and elemental analyses. The obtained quaternized phthalocyanines (, , and ) showed amphiphilic behaviour with excellent solubility in both organic and aqueous solutions, which makes them potential photosensitizers for use in photodynamic therapy (PDT) of cancer. The photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen and photodegradation quantum yields) properties of these novel phthalocyanines were studied in DMSO for both non-ionic and ionic quaternized derivatives. However, these properties were examined in both DMSO and phosphate buffer solution (PBS) for quaternized ionic phthalocyanines. The effects of the positions of substituents (peripheral or non-peripheral) and the quaternization of the nitrogen atoms on the substituents about their photophysical and photochemical properties were also compared in this study. The bovine serum albumin (BSA) binding behaviours of the studied quaternized ionic zinc(ii) phthalocyanines were also described in PBS solutions. The quaternized phthalocyanines (, , and ) successfully displayed light-dependent photodamage in HeLa and HuH-7 cancer cells in photodynamic therapy treatment. The photosensitivity and the intensity of damage were found directly related to the concentration of the photosensitizers. PMID:25923925
Synthesis and Characterization of Rare Earth Corrole-Phthalocyanine Heteroleptic Triple-Decker Complexes.
Lu, Guifen; Li, Jing; Yan, Sen; Zhu, Weihua; Ou, Zhongping; Kadish, Karl M
We recently reported the first example of a europium triple-decker tetrapyrrole with mixed corrole and phthalocyanine macrocycles and have now extended the synthetic method to prepare a series of rare earth corrole-phthalocyanine heteroleptic triple-decker complexes, which are characterized by spectroscopic and electrochemical methods. The examined complexes are represented as M2[Pc(OC4H9)8]2[Cor(ClPh)3], where Pc = phthalocyanine, Cor = corrole, and M is Pr(III), Nd(III), Sm(III), Eu(III), Gd(III), or Tb(III). The Y(III) derivative with OC4H9 Pc substituents was obtained in too low a yield to characterize, but for the purpose of comparison, Y2[Pc(OC5H11)8]2[Cor(ClPh)3] was synthesized and characterized in a similar manner. The molecular structure of Eu2[Pc(OC4H9)8]2[Cor(ClPh)3] was determined by single-crystal X-ray diffraction and showed the corrole to be the central macrocycle of the triple-decker unit with a phthalocyanine on each end. Each triple-decker complex undergoes up to eight reversible or quasireversible one-electron oxidations and reductions with E1/2 values being linearly related to the ionic radius of the central ions. The energy (E) of the main Q-band is also linearly related to the radius of the metal. Comparisons are made between the physicochemical properties of the newly synthesized mixed corrole-phthalocyanine complexes and previously characterized double- and triple-decker derivatives with phthalocyanine and/or porphyrin macrocycles. PMID:26020355
[The monomer electronic spectra and fluorescence spectra of some metal phthalocyanines].
Huang, J; Liu, E; Yang, S; Chen, N; Huang, J; Duan, J; Chen, Y
The monomer electronic absorption spectra of the ZnPcS2P2 (disulfonated diphthalimidomethyl phthalocyanine zinc) in 11 kinds of solvents and 5 kinds of unsubstituted metal phthalocyanines in DMF were investigated. The monomer electronic absorption spectra of some substituted phthalocyanine zinc including ZnPcS4 (tetrasulfonated phthalocyanine zinc), ZnPcS4 (tetraphthalimidomethyl phthalocyanine zinc), ZnPc(NO2)4 (tetranitro phthalocyanine zinc) and ZnPcS2P2 in the same solvent were also studied. The result showed that (1) with the strengthening of coordination ability of the solvent, the maximum absorption wavelength of ZnPcS2P2 increased slightly. (2) with the increasing of electronegativity of central ion, the maximum absorption wavelength of MPcs had a little blue shift. (3) the electron-donating substituting group caused slightly blue shift. The monomer fluorescence spectra of ZnPcS4, ZnPcP4, and ZnPcS2P2 in different solvents were determined. The result showed that (1) the electron-withdrawing substituting group caused slightly red shift of the fluorescence spectra. (2) with the strenghtening of coordination ability of the solvent, the maximum emission wavelength increased slightly. (3) the fluorescence intensity of ZnPcS2P2 in the solution which contains Cremophor EL was remarkable stronger than that in other solvents. This is an important suggest to the development of photodynamic diagnose agent. The effect of solvents, central ions and substituents on spectra were partly explained by means of the quantrum chemistry. PMID:12953463
Plasma Protein Binding of Amphotericin B and Pharmacokinetics of Bound versus Unbound Amphotericin B after Administration of Intravenous Liposomal Amphotericin B (AmBisome) and Amphotericin B Deoxycholate
Ihor Bekersky; Robert M. Fielding; Dawna E. Dressler; Jean W. Lee; Donald N. Buell; Thomas J. Walsh
Unilamellar liposomal amphotericin B (AmBisome) (liposomal AMB) reduces the toxicity of this antifungal drug. The unique composition of liposomal AMB stabilizes the liposomes, producing higher sustained drug levels in plasma and reducing renal and hepatic excretion. When liposomes release their drug payload, unbound, protein-bound, and liposomal drug pools may exist simultaneously in the body. To determine the amounts of drug
Theoretical modelling of exchange interactions in metal-phthalocyanines
NASA Astrophysics Data System (ADS)
Wu, Wei; Fisher, Andrew; Harrison, Nic; Serri, Michele; Wu, Zhenlin; Heutz, Sandrine; Jones, Tim; Aeppli, Gabriel
The theoretical understanding of exchange interactions in organics provides a key foundation for quantum molecular magnetism. Recent SQUID magnetometry of a well know organic semiconductor, copper-phthalocyanine [1,2] (CuPc) shows that it forms quasi-one-dimensional spin chains. Green's function perturbation theory calculation [3] is used to find the dominant exchange mechanism. Hybrid density functional theory simulations [4] give a quantitative insight to exchange interactions and electronic structures. Both calculations are performed for different stacking and sliding angles for lithium-Pc, cobalt-Pc, chromium-Pc, and copper-Pc. The exchange interactions depend strongly on stacking angles, but weakly on sliding angles. Our results qualitatively agree with the experiments, and remarkably ?-cobalt-Pc has a very large exchange above liquid-Nitrogen temperature. Our theoretical predictions on the exchange interactions can guide experimentalists to design novel organic semiconductors. [0pt] [1] S. Heutz, et. al., Adv. Mat., 19, 3618 (2007) [2] Hai Wang, et. al., ACS Nano, 4, 3921 (2010) [3] Wei Wu, et. al., Phys. Rev. B 77, 184403 (2008) [4] Wei Wu, et. al., Phys. Rev. B 84, 024427 (2011)
Mixed configuration ground state in iron(II) phthalocyanine
NASA Astrophysics Data System (ADS)
Fernández-Rodríguez, Javier; Toby, Brian; van Veenendaal, Michel
We calculate the angular dependence of the x-ray linear and circular dichroism at the L2 ,3 edges of ? -Fe(II) Phthalocyanine (FePc) thin films using a ligand-field model with full configuration interaction. We find the best agreement with the experimental spectra for a mixed ground state of 3Eg(a1g 2eg3b2g 1) and 3B2 g(a1g 1eg4b2g 1) with the two configurations coupled by the spin-orbit interaction. The 3Eg(b ) and 3B2 g states have easy-axis and easy-plane anisotropies, respectively. Our model accounts for an easy-plane magnetic anisotropy and the measured magnitudes of the in-plane orbital and spin moments. The proximity in energy of the two configurations allows a switching of the magnetic anisotropy from easy plane to easy axis with a small change in the crystal field, as recently observed for FePc adsorbed on an oxidized Cu surface. We also discuss the possibility of a quintet ground state (5A1 g is 250 meV above the ground state) with planar anisotropy by manipulation of the Fe-C bond length by depositing the complex on a substrate that is subjected to a mechanical strain.
Regiospecific synthesis of tetrasubstituted phthalocyanines and their liquid crystalline order.
Apostol, Petru; Bentaleb, Ahmed; Rajaoarivelo, Mbolotiana; Clérac, Rodolphe; Bock, Harald
Metal-free and metal(II) all-endo-tetraalkoxy-phthalocyanines of C4h symmetry are synthesised regiospecifically from 3-(2-butyloctyloxy)phthalonitrile with lithium octanolate and subsequent metal ion exchange. The voluminous, yet not overly large, and racemically disordered alkoxy substituent not only renders the cyclotetramerisation regiospecific, but also leads to liquid crystalline self-assembly with attainable clearing temperatures and persisting columnar organisation at room temperature. A rare hexagonal mesophase with twelve columns per hexagonal unit cell is found in the metal-free homologue, whereas the metal complexes show rectangular mesophases. The clearing temperature increases with increasing axial component of the metal ion coordination sphere. At low temperature, significant antiferromagnetic exchange between magnetic centres is observed for the Co(II) homologue, whereas the magnetic centres are magnetically independent in the Cu(II) derivative, in line with the observed higher clearing temperature in the Co(II) case that testifies of stronger interdisk interactions. PMID:25697075
Commensurism at electronically weakly interacting phthalocyanine/PTCDA heterointerfaces
NASA Astrophysics Data System (ADS)
Gruenewald, Marco; Sauer, Christoph; Peuker, Julia; Meissner, Matthias; Sojka, Falko; Schöll, Achim; Reinert, Friedrich; Forker, Roman; Fritz, Torsten
Interfaces in multilayered electronic devices are of paramount importance, especially for layer thicknesses in the nanometer range. Among the interfacial processes are charge injection or extraction and excitonic dissociation, the latter being particularly relevant if molecular components are involved. Highly ordered superstructures are preferable to prevent undesired losses of charge carriers and/or excitons. Epitaxial organic-inorganic systems have already received eminent attention, but only few studies have dealt with organic-organic heterointerfaces so far. Here, we focus on the adsorption of metal-phthalocyanines (MePc, Me = Sn or Cu) on 3,4,9,10-perylene-tetracarboxylic-dianhydride (PTCDA) in the form of stacked monolayers (ML) on Ag(111). Using scanning tunneling microscopy and low-energy electron diffraction we reveal an initial nonordered growth for dilute SnPc submonolayers and consecutively three condensed phases at coverages ranging up to 1 ML —each possessing a distinct commensurate registry with the underlying PTCDA. By applying in situ optical differential reflectance spectroscopy and photoelectron spectroscopy we find that neither the SnPc nor the CuPc phases exhibit significant electronic or optical coupling with the PTCDA interlayer. Therefore, our results demonstrate that commensurism does not necessarily imply chemisorption, as stated previously in the literature, but that physisorption may be accompanied by commensurate superstructures.
Decomposition of propylene carbonate in a lithium/metal phthalocyanine cell
Arakawa, M.; Yamaki, J.; Okada, T.
Experimental results from a study of the catalytic effect of metal phthalocyanine (MPc) on the gas evolution reaction in Li batteries are reported. The trials comprised galvanostatic discharge tests with a battery containing a Li anode, an MPc cathode and a reference electrode. A gas evolution curve was generated, and further tests were performed with a cell containing FePc to investigate the gas evolution reaction more quickly. The gas evolved was proportional to the discharge capacity and featured propylene as the chief component. The appearance of propylene was attributed to a reaction between Pc and the discharge product of phthalocyanine. 9 references.
Influence of film thickness and air exposure on the transport gap of manganese phthalocyanine
Haidu, F.; Fechner, A.; Salvan, G.; Gordan, O. D.; Fronk, M.; Zahn, D. R. T. [Semiconductor Physics, Chemnitz University of Technology, D-09107 Chemnitz (Germany); Lehmann, D. [Semiconductor Physics, Chemnitz University of Technology, D-09107 Chemnitz (Germany); INNOVENT Technology Development, D-07745 Jena (Germany); Mahns, B.; Knupfer, M. [Electronic and Optical Properties Department, IFW Dresden, D-01171 Dresden (Germany)
The interface formation between manganese phthalocyanine (MnPc) and cobalt was investigated combining ultraviolet photoelectron spectroscopy and inverse photoelectron spectroscopy. The transport band gap of the MnPc increases with the film thickness up to a value of (1.2 {+-} 0.3) eV while the optical band gap as determined from spectroscopic ellipsometry amounts to 0.5 eV. The gap values are smaller compared to other phthalocyanines due to metallic Mn 3d states close to the Fermi level. The transport band gap was found to open upon air exposure as a result of the disappearance of the occupied 3d electronic states.
[Liposomal boron delivery system for neutron capture therapy].
Nakamura, Hiroyuki
Boron neutron capture therapy (BNCT) is a binary cancer treatment based on the nuclear reaction of two essentially nontoxic species, (10)B and thermal neutrons. High accumulation and selective delivery of boron into tumor tissue are the most important requirements to achieve efficient neutron capture therapy of cancers. This review focuses on the liposomal boron delivery system (BDS) as a recent promising approach that meets these requirements for BNCT. BDS involves two strategies: (1) encapsulation of boron in the aqueous core of liposomes and (2) accumulation of boron in the liposomal bilayer. Various boronated liposomes have been developed and significant boron accumulation into tumor tissue with high tumor/blood boron ratios has been achieved by BDS. PMID:18239367
Elastic liposomes containing benzophenone-3 for sun protection factor enhancement.
Severino, Patrícia; Moraes, Lívia Faria; Zanchetta, Beatriz; Souto, Eliana B; Santana, Maria H A
This work was focused on the loading of benzophenone-3 in elastic liposomes composed of egg phosphatidylcholine and cholesterol, prepared by the Bangham method. Samples were characterized in terms of particle size, polydispersity index (PI), zeta potential, encapsulation efficiency and in vitro photoprotection properties. The extrusion of liposomes loading benzophenone-3 produced reduced-size (100 nm) elastic liposomes with a PI of 0.2. The active was loaded with a concentration of 20.34% (m/m) revealing changes in the ultraviolet properties after loading. On the basis of these results, it can be anticipated that liposomes are able to improve sun protector factor in vitro compared the free active. PMID:21563987
Treatment of Visceral Leishmaniasis with Sterically Stabilized Liposomes Containing Camptothecin
Proulx, Marie-Eve; Désormeaux, André; Marquis, Jean-François; Olivier, Martin; Bergeron, Michel G.
The efficacy of 20(S)-camptothecin (CPT), free and incorporated into sterically stabilized liposomes, has been investigated in vitro against Leishmania donovani promastigotes and in vivo in a murine model of visceral leishmaniasis. Incubation of L. donovani promastigotes with free or liposomal CPT inhibited the growth of parasites in a dose-dependent manner. Tissue distribution studies revealed that the intraperitoneal administration of liposomal CPT was efficient for the delivery of high drug levels to the liver and spleen. Treatment of infected mice with intraperitoneal injections of free and liposomal CPT significantly reduced the parasite loads in the livers by 43 and 55%, respectively, compared with the loads for untreated controls. However, both treatments caused normochromic anemia and neutropenia. PMID:11502539
Remote loading of preencapsulated drugs into stealth liposomes
Sur, Surojit; Fries, Anja C.; Kinzler, Kenneth W.; Zhou, Shibin; Vogelstein, Bert
Loading drugs into carriers such as liposomes can increase the therapeutic ratio by reducing drug concentrations in normal tissues and raising their concentrations in tumors. Although this strategy has proven advantageous in certain circumstances, many drugs are highly hydrophobic and nonionizable and cannot be loaded into liposomes through conventional means. We hypothesized that such drugs could be actively loaded into liposomes by encapsulating them into specially designed cyclodextrins. To test this hypothesis, two hydrophobic drugs that had failed phase II clinical trials because of excess toxicity at deliverable doses were evaluated. In both cases, the drugs could be remotely loaded into liposomes after their encapsulation (preloading) into cyclodextrins and administered to mice at higher doses and with greater efficacy than possible with the free drugs. PMID:24474802
Atmospheric-pressure guided streamers for liposomal membrane disruption
Svarnas, P.; Aleiferis, Sp. [High Voltage Laboratory, Department of Electrical and Computer Engineering, University of Patras, Rion 26504 (Greece); Matrali, S. H. [Pharmaceutical Technology Laboratory, Department of Pharmacy, University of Patras, Rion 26504 (Greece); Gazeli, K. [High Voltage Laboratory, Department of Electrical and Computer Engineering, University of Patras, Rion 26504 (Greece); IPREM-LCABIE, Plasmas et Applications, UPPA, 64000 Pau (France); Clement, F. [IPREM-LCABIE, Plasmas et Applications, UPPA, 64000 Pau (France); Antimisiaris, S. G. [Pharmaceutical Technology Laboratory, Department of Pharmacy, University of Patras, Rion 26504 (Greece); Institute of Chemical Engineering Sciences (ICES)-FORTH, Rion 26504 (Greece)
The potential to use liposomes (LIPs) as a cellular model in order to study interactions of cold atmospheric-pressure plasma with cells is herein investigated. Cold atmospheric-pressure plasma is formed by a dielectric-barrier discharge reactor. Large multilamellar vesicle liposomes, consisted of phosphatidylcholine and cholesterol, are prepared by the thin film hydration technique, to encapsulate a small hydrophilic dye, i.e., calcein. The plasma-induced release of calcein from liposomes is then used as a measure of liposome membrane integrity and, consequently, interaction between the cold atmospheric plasma and lipid bilayers. Physical mechanisms leading to membrane disruption are suggested, based on the plasma characterization including gas temperature calculation.
Acoustical properties of individual liposome-loaded microbubbles.
Luan, Ying; Faez, Telli; Gelderblom, Erik; Skachkov, Ilya; Geers, Bart; Lentacker, Ine; van der Steen, Ton; Versluis, Michel; de Jong, Nico
A comparison between phospholipid-coated microbubbles with and without liposomes attached to the microbubble surface was performed using the ultra-high-speed imaging camera (Brandaris 128). We investigated 73 liposome-loaded microbubbles (loaded microbubbles) and 41 microbubbles without liposome loading (unloaded microbubbles) with a diameter ranging from 3-10 ?m at frequencies ranging from 0.6-3.8 MHz and acoustic pressures ranging from 5-100 kPa. The experimental data showed nearly the same shell elasticity for the loaded and unloaded bubbles, but the shell viscosity was higher for loaded bubbles compared with unloaded bubbles. For loaded bubbles, a higher pressure threshold for the bubble vibrations was noticed. In addition, an "expansion-only" behavior was observed for up to 69% of the investigated loaded bubbles, which mostly occurred at low acoustic pressures (?30 kPa). Finally, fluorescence imaging showed heterogeneity of liposome distributions of the loaded bubbles. PMID:23196203
Interaction of curcumin with lipid monolayers and liposomal bilayers.
Karewicz, Anna; Bielska, Dorota; Gzyl-Malcher, Barbara; Kepczynski, Mariusz; Lach, Rados?aw; Nowakowska, Maria
Curcumin shows huge potential as an anticancer and anti-inflammatory agent. However, to achieve a satisfactory bioavailability and stability of this compound, its liposomal form is preferable. Our detailed studies on the curcumin interaction with lipid membranes are aimed to obtain better understanding of the mechanism and eventually to improve the efficiency of curcumin delivery to cells. Egg yolk phosphatidylcholine (EYPC) one-component monolayers and bilayers, as well as mixed systems containing additionally dihexadecyl phosphate (DHP) and cholesterol, were studied. Curcumin binding constant to EYPC liposomes was determined based on two different methods: UV/Vis absorption and fluorescence measurements to be 4.26×10(4)M(-1) and 3.79×10(4)M(-1), respectively. The fluorescence quenching experiment revealed that curcumin locates in the hydrophobic region of EYPC liposomal bilayer. It was shown that curcumin impacts the size and stability of the liposomal carriers significantly. Loaded into the EYPC/DPH/cholesterol liposomal bilayer curcumin stabilizes the system proportionally to its content, while the EYPC/DPH system is destabilized upon drug loading. The three-component lipid composition of the liposome seems to be the most promising system for curcumin delivery. An interaction of free and liposomal curcumin with EYPC and mixed monolayers was also studied using Langmuir balance measurements. Monolayer systems were treated as a simple model of cell membrane. Condensing effect of curcumin on EYPC and EYPC/DHP monolayers and loosening influence on EYPC/DHP/chol ones were observed. It was also demonstrated that curcumin-loaded EYPC liposomes are more stable upon interaction with the model lipid membrane than the unloaded ones. PMID:21778041
Liposome-mediated gene transfer to lung isografts
Carlos H. R. Boasquevisque; Teng C. Lee; Bassem N. Mora; David Peterson; William O. Osburn; Matthew Bernstein; Wei Zhang; Jennifer B. Nietupski; Ronald K. Scheule; Joel D. Cooper; Mitchell D. Botney; G. Alexander Patterson
Objectives: Our objectives were to determine the feasibility, efficacy, and safety of in vivo and ex vivo liposome-mediated gene transfer to lung isografts.Methods: Fischer rats were divided into three main groups: (1) Nontransplant setting: Liposome–chloramphenicol acetyl transferase cDNA was intravenously injected, and lungs were harvested at different time points: 2, 6, 12, and 24 hours; 2, 5, 8, and 21
Marine lipid-based liposomes increase in vivo FA bioavailability
Maud Cansell; Fabienne Nacka; Nicole Combe
Liposomes made from an extract of natural marine lipids and containing a high n-3 PUFA lipid ratio were envisaged as oral\\u000a route vectors for FA supplements in order to increase PUFA bioavailability. The absorption of FA in thoracic lymph duct-cannulated\\u000a rats, after intragastric feeding of dietary fats in the form of liposomes or fish oil, was compared. Lipid and FA
Synthetic liposomes are protective from bleomycin-induced lung toxicity
Gwinn, William M.; Kapita, Mayanga C.; Wang, Ping M.; Cesta, Mark F.
Idiopathic pulmonary fibrosis is a devastating disease characterized by a progressive, irreversible, and ultimately lethal form of lung fibrosis. Except for lung transplantation, no effective treatment options currently exist. The bleomycin animal model is one of the best studied models of lung injury and fibrosis. A previous study using mouse tumor models observed that liposome-encapsulated bleomycin exhibited reduced lung toxicity. Therefore, we hypothesized that airway delivery of synthetic phosphatidylcholine-containing liposomes alone would protect mice from bleomycin-induced lung toxicity. C57BL/6 mice were administered uncharged multilamellar liposomes (100 ?l) or PBS vehicle on day 0 by airway delivery. Bleomycin (3.33 U/kg) or saline vehicle was then given intratracheally on day 1 followed by four additional separate doses of liposomes on days 4, 8, 12, and 16. Fluorescent images of liposomes labeled with 1,1?-dioctadecyl-3,3,3?,3? tetramethylindocarbocyanine perchlorate confirmed effective and widespread delivery of liposomes to the lower respiratory tract as well as uptake primarily by alveolar macrophages and to a lesser extent by type II alveolar epithelial cells. Results at day 22, 3 wk after bleomycin treatment, showed that airway delivery of liposomes before and after intratracheal administration of bleomycin significantly reduced bleomycin-induced lung toxicity as evidenced by less body weight loss, chronic lung inflammation, and fibrosis as well as improved lung compliance compared with controls. These data indicate that airway-delivered synthetic liposomes represent a novel treatment strategy to reduce the lung toxicity associated with bleomycin in a mouse model. PMID:21602446
Vaccination with liposome–DNA complexes elicits enhanced antitumor immunity
L U'Ren; R Kedl; S Dow
Cationic liposomes have been shown to potentiate markedly the ability of plasmid DNA to activate innate immune responses. We reasoned therefore that liposome–DNA complexes (LDC) could be used to produce more effective plasmid DNA vaccines for cancer. To test this hypothesis, tumor-bearing mice were vaccinated with conventional plasmid DNA vaccines or with LDC vaccines encoding model tumor antigens and CD8+
Photosensitive liposomes as potential drug delivery vehicles for photodynamic therapy
NASA Astrophysics Data System (ADS)
Morgan, Christopher G.; Mitchell, A. C.; Chowdhary, R. K.
Light-sensitive liposomes incorporating a photochromic phospholipid (Bis-Azo PC) have been developed which exhibit light-activated release of entrapped contents and intervesicular fusion. The trapping and light-induced release of inorganic ions, fluorescent market dyes, and the antitumor drug methotrexate have been demonstrated. These results are discussed together with some of the potential therapeutic applications of light-sensitive liposomes.
Liposomal delivery system enhances anti-inflammatory properties of curcumin.
Basnet, Purusotam; Hussain, Haider; Tho, Ingunn; Skalko-Basnet, Natasa
Curcumin is a well-established natural antioxidant and anti-inflammatory agent. Up till now its potential in treatment of vaginal inflammation has not been evaluated. We are aiming at developing liposomal delivery system for curcumin targeting vaginal administration. Liposomes as nanosized phospholipid-based vesicles are expected to solubilize curcumin and enhance its activity, thus serving as an advanced topical formulation in the treatment of vaginal inflammation. Curcumin and curcuminoids were analyzed by the high-performance liquid chromatography method. Liposomes containing curcumin/curcuminoids of various sizes were prepared and characterized. Antioxidant activities of curcumin and liposomal curcumin were compared based on 1,1-diphenyl-2-picrylhydrazyl radical scavenging and superoxide dismutase activities. The anti-inflammatory activities were determined by measuring the inhibition of lipopolysaccharide -induced nitric oxide, interleukin-1?, and tumor necrosis factor-? production in macrophage RAW 264.7 cells. Curcumin/curcuminoids were encapsulated in phosphatidylcholine vesicles with high yields. Vesicles in the size range around 200 nm were selected for stability and cell experiments. Liposomal curcumin were found to be twofold to sixfold more potent than corresponding curcuminoids. Moreover, the mixture of curcuminoids was found to be more potent than pure curcumin in regard to the antioxidant and anti-inflammatory activities. Liposomal delivery systems for curcumin are promising formulations for the treatment of vaginal inflammation. PMID:21989712
The Antimicrobial Activity of Liposomal Lauric Acids Against Propionibacterium acnes
Yang, Darren; Pornpattananangkul, Dissaya; Nakatsuji, Teruaki; Chan, Michael; Carson, Dennis; Huang, Chun-Ming; Zhang, Liangfang
This study evaluated the antimicrobial activity of lauric acid (LA) and its liposomal derivatives against Propionibacterium acnes (P. acnes), the bacterium that promotes inflammatory acne. First, the antimicrobial study of three free fatty acids (lauric acid, palmitic acid and oleic acid) demonstrated that LA gives the strongest bactericidal activity against P. acnes. However, a setback of using LA as a potential treatment for inflammatory acne is its poor water solubility. Then the LA was incorporated into a liposome formulation to aid its delivery to P. acnes. It's demonstrated that the antimicrobial activity of LA was not only well maintained in its liposomal derivatives but also enhanced at low LA concentration. In addition, the antimicrobial activity of LA-loaded liposomes (LipoLA) mainly depended on the LA loading concentration per single liposomes. Further study found that the LipoLA could fuse with the membranes of P. acnes and release the carried LA directly into the bacterial membranes, thereby killing the bacteria effectively. Since LA is a natural compound that is the main acid in coconut oil and also resides in human breast milk and liposomes have been successfully and widely applied as a drug delivery vehicle in the clinic, the LipoLA developed in this work holds great potential of becoming an innate, safe and effective therapeutic medication for acne vulgaris and other P. acnes associated diseases. PMID:19665786
Folate receptor targeted liposomes encapsulating anti-cancer drugs.
Chaudhury, Anumita; Das, Surajit
Among all available lipid based nanoparticulate systems, the success of liposomal drug delivery system is evident by the number of liposomal products available in the market or under advanced stages of preclinical and clinical trials. Liposome has the ability to deliver chemotherapeutic agents to the targeted tissues or even inside the cancerous cells by enhanced intracellular penetration or improved tumour targeting. In the last decade, folate receptor mediated tumour targeting has emerged as an attractive alternative method of active targeting of cancer cells through liposomes due to its numerous advantages over other targeting methods. Folate receptors, also known as folate binding proteins, allow the binding and internalization of folate or folic acid into the cells by a method called folate receptor mediated endocytosis. They have restricted presence in normal cells and are mostly expressed during malignant transformation. In this review article, folate receptor targeting capability of liposomes has been described. This review article has focussed on the different cancer drugs which have been encapsulated in folate receptor targeted liposomes and their in vitro as well as in vivo efficacies in several tumour models. PMID:25601598
Polydopamine/liposome coatings and their interaction with myoblast cells.
Lynge, Martin E; Ogaki, Ryosuke; Laursen, Anja Overgĺrd; Lovmand, Jette; Sutherland, Duncan S; Städler, Brigitte
Surface-mediated drug delivery is a recent concept, where active surface coatings are employed to deliver therapeutic cargo to cells. Herein, we explore the potential of liposomes embedded in polydopamine (PDA) coatings to serve as drug deposits stored on planar substrates. We quantify the PDA growth rate on glass by XPS and show that PDA coatings support myoblast adherence and proliferation. Further, PDA capping layers were deposited on glass substrates precoated with poly(L-lysine) and zwitterionic liposomes. Already thin PDA capping layers render liposome coated surfaces cell adhesive. We experimentally show for the first time, the internalization of a model hydrophobic cargo, that is, fluorescent lipids embedded within the lipid bilayer of liposomes by the cells from the surface. This is evident from the fluorescence exhibited by the cells grown on PDA coatings containing fluorescently labeled liposomes, with the highest fluorescent intensity found in the close proximity of the cell nuclei. The cargo uptake efficiency depends on the thickness of the PDA capping layer and the cell residence time on the coated substrates. Taken together, we demonstrate the first step toward the establishment of a versatile approach using liposomal drug deposits in polymer thin films for surface-mediated drug delivery. PMID:21539399
Protrusive growth from giant liposomes driven by actin polymerization
Miyata, Hidetake; Nishiyama, Shuji; Akashi, Ken-ichirou; Kinosita, Kazuhiko
Development of protrusions in the cell is indispensable in the process of cell motility. Membrane protrusion has long been suggested to occur as a result of actin polymerization immediately beneath the cell membrane at the leading edge, but elucidation of the mechanism is insufficient because of the complexity of the cell. To study the mechanism, we prepared giant liposomes containing monomeric actin (100 or 200 ?M) and introduced KCl into individual liposomes by an electroporation technique. On the electroporation, the giant liposomes deformed. Most importantly, protrusive structure grew from the liposomes containing 200 ?M actin at rates (ranging from 0.3 to 0.7 ?m/s) similar to those obtained in the cell. The deformation occurred in a time range (30 ? 100 s) similar to that of actin polymerization monitored in a cuvette (ca. 50 s). Concomitant with deformation, Brownian motion of micron-sized particles entrapped in the liposomes almost ceased. From these observations, we conclude that actin polymerization in the liposomes caused the protrusive formation. PMID:10051592
Molecular targeting of liposomal nanoparticles to tumor microenvironment
Zhao, Gang; Rodriguez, B Leticia
Liposomes are biodegradable and can be used to deliver drugs at a much higher concentration in tumor tissues than in normal tissues. Both passive and active drug delivery by liposomal nanoparticles can significantly reduce the toxic side effects of anticancer drugs and enhance the therapeutic efficacy of the drugs delivered. Active liposomal targeting to tumors is achieved by recognizing specific tumor receptors through tumor-specific ligands or antibodies coupled onto the surface of the liposomes, or by stimulus-sensitive drug carriers such as acid-triggered release or enzyme-triggered drug release. Tumors are often composed of tumor cells and nontumor cells, which include endothelial cells, pericytes, fibroblasts, stromal, mesenchymal cells, innate, and adaptive immune cells. These nontumor cells thus form the tumor microenvironment, which could be targeted and modified so that it is unfavorable for tumor cells to grow. In this review, we briefly summarized articles that had taken advantage of liposomal nanoparticles as a carrier to deliver anticancer drugs to the tumor microenvironment, and how they overcame obstacles such as nonspecific uptake, interaction with components in blood, and toxicity. Special attention is devoted to the liposomal targeting of anticancer drugs to the endothelium of tumor neovasculature, tumor associated macrophages, fibroblasts, and pericytes within the tumor microenvironment. PMID:23293520
Click modification of multifunctional liposomes bearing hyperbranched polyether chains.
Fritz, Thomas; Hirsch, Markus; Richter, Felix C; Müller, Sophie S; Hofmann, Anna M; Rusitzka, Kristiane A K; Markl, Jürgen; Massing, Ulrich; Frey, Holger; Helm, Mark
Aiming at controlled modification of liposomal surface structures, we describe a postpreparational approach for surface derivatization of a new type of multifunctional, sterically stabilized liposomes. Application of dual centrifugation (DC) resulted in high encapsulation efficiencies above 50% at very small batch sizes with a total volume of 150 ?L, which were conductive to fast and efficient optimization of variegated surface modification reactions. Cholesterol-polymer amphiphiles, including complex hyperbranched polyether structures bearing 1-4 terminal alkynes, were used in DC formulations to provide steric stabilization. The alkyne moieties were explored as anchors for the conjugation of small molecules to the liposomal surface via click chemistry, binding 350-450 fluorophores per liposome as examples for surface active molecules. Using Förster resonance energy transfer (FRET) spectroscopy, the conjugation reaction as well as the uptake of FRET-labeled liposomes by RBE4 cells was monitored, and the distribution of the fluorescent lipids among cellular structures and membranes could be studied. Thus, the combination of clickable hyperbranched amphiphiles and dual centrifugation provides access to well-defined liposomal formulations with a variety of surface moieties. PMID:24805163
Liposome distribution after intravenous and selective intraarterial infusion in dogs
Wright, K.C.; Kasi, L.P.; Jahns, M.S.; Hashimoto, S.; Wallace, S. (Univ. of Texas M.D. Anderson Cancer Center, Houston (USA))
In an effort to improve hepatic uptake of liposomes for drug delivery, empty vesicles were administered by means of selective arterial infusion. Negatively charged, multilamellar liposomes were labeled with technetium-99m and infused into healthy adult dogs. Each dog received 100 mg/m2 of lipid over 10 minutes at 2 mL/min. Liposomes were administered via the common hepatic artery after proximal occlusion of the gastroduodenal artery, via the cranial mesenteric artery, and via the cephalic vein. Distribution (liver, spleen, and lungs) was determined by computer-assisted external imaging techniques. On the average, after arterial infusion, 69.2% of the total activity was located in the liver, 3.6% in the spleen, 3.2% in the lungs, and 3.5% in the general circulation. Following venous injection, 50.7% of the radioactivity was found in the liver, 9.1% in the spleen, 8.6% in the lungs, and 6.7% in the peripheral blood. Once the liposomes entered the systemic circulation, they were cleared at the same rate (half-life beta = 21.5 hours) independent of their route of administration. Increased hepatic liposome uptake should translate into higher local and lower systemic liposomal drug levels.
Long-circulating, pH-sensitive liposomes.
Momekova, Denitsa; Rangelov, Stanislav; Lambov, Nikolay
A major limiting factor for the wide application of pH-sensitive liposomes is their recognition and sequestration by the phagocytes of the reticulo-endothelial system, which conditions a very short circulation half-life. Typically prolonged circulation of liposomes is achieved by grafting their membranes with pegylated phospholipids (PEG-lipids), which have been shown, however, to deteriorate membrane integrity on one hand and to hamper the pH-responsiveness on the other. Hence, the need for novel alternative surface modifying agents to ensure effective half-life prolongation of pH-sensitive liposomes is a subject of intensive research. A series of copolymers having short blocks of lipid-mimetic units has been shown to sterically stabilize conventional liposomes based on different phospholipids. This has prompted us to broaden their utilization to pH-sensitive liposomes, too. The present contribution gives thorough account on the chemical synthesis of these copolymers their incorporation in DOPE:CHEMs pH-sensitive liposomes and detailed explanation on the battery of techniques for the biopharmaceutical characterization of the prepared formulations in terms of pH-responsiveness, cellular internalization, in vivo pharmacokinetics and biodistribution. PMID:20072904
Modification of wool surface by liposomes for dyeing with weld.
Montazer, Majid; Zolfaghari, Alireza; Toliat, Taibeh; Moghadam, Mohammad Bameni
In this research work, wool surface has been modified by liposome to investigate its effects on dyeing with weld, a yellow natural dye. To do this, samples were first treated with aluminium sulphate and afterward with different concentrations of liposomes at various temperatures for 30 minutes and, finally, dyed with weld at 75, 85, and 95 degrees C for 30, 45, and 60 minutes. K/S values of fabric samples were calculated and washing, light and rub fastness properties of the samples were indicated. The results proposed that the sample treated with 1% liposomes and dyed at 75 degrees C for 60 min has the highest K/S value. The central composite design (CCD) used for the experimental plan with three variables on the results of color strength and statistical analysis confirms the optimum conditions obtained by the experimental results. It was also found that washing, light, wet, and dry rub fastness properties of samples dyed with weld, including liposomes, have not significantly changed. The results of water drop absorption indicated that the hydrophobicity is higher for the samples pretreated with liposomes. The SEM picture of wool sample treated with mordant and liposomes and finally dyed with weld shows a coated layer on the fiber surface. PMID:19552578
Size of thermosensitive liposomes influences content release.
Hossann, Martin; Wang, Tungte; Wiggenhorn, Michael; Schmidt, Rebecca; Zengerle, Anja; Winter, Gerhard; Eibl, Hansjörg; Peller, Michael; Reiser, Maximilian; Issels, Rolf D; Lindner, Lars H
Thermosensitive liposomes (TSL) in combination with regional hyperthermia represent a powerful tool for tumor specific drug delivery. The objective of this study was to investigate the influence of vesicle size on the biophysical properties of TSL. TSL were composed of DPPC/DSPC/1,2-dipalmitoyl-sn-glycero-3-phosphoglyceroglycerol (DPPG(2)) 50:20:30 (mol/mol) (DPPG(2)-TSL) and DPPC/P-Lyso-PC/DSPE-PEG2000 90:10:4 (mol/mol) (PEG/Lyso-TSL) with encapsulated fluorescent dye carboxyfluorescein, anticancer drug doxorubicin or magnetic resonance contrast agent gadodiamide. Extrusion was performed with polycarbonate filters of distinct pore size to obtain TSL with different diameters (50 to 200nm). Phase transition temperature (T(m)) of the bilayer forming phospholipids was not influenced by vesicle size in the tested range. However, vesicle size had a major impact on in vitro content release properties of TSL in the investigated temperature range between 30 and 45°C. Generally, vesicle size was inversely related to content release properties with increased content release rates for decreased vesicle sizes. Size dependency of content release properties varied between all tested formulations and DPPG(2)-TSL were generally less affected by size changes in the range of 100 to 150nm as compared to PEG/Lyso-TSL. Independent from gadodiamide release, vesicle size influenced the signal intensity of DPPG(2)-TSL also at temperatures below T(m) due to improved water exchange for smaller vesicles. Liposomes around 100nm in size are routinely used in vivo, hence a quality control for TSL preparations is required prior to use. Even small changes in size or a wider size distribution might affect stability and release properties and thus yield in decreased efficacy or unwanted side effects of drug loaded TSL during in vivo applications. PMID:20727921
The combined effect of encapsulating curcumin and C6 ceramide in liposomal nanoparticles against osteosarcoma.
Dhule, Santosh S; Penfornis, Patrice; He, Jibao; Harris, Michael R; Terry, Treniece; John, Vijay; Pochampally, Radhika
This study examines the antitumor potential of curcumin and C6 ceramide (C6) against osteosarcoma (OS) cell lines when both are encapsulated in the bilayer of liposomal nanoparticles. Three liposomal formulations were prepared: curcumin liposomes, C6 liposomes and C6-curcumin liposomes. Curcumin in combination with C6 showed 1.5 times enhanced cytotoxic effect in the case of MG-63 and KHOS OS cell lines, in comparison with curcumin liposomes alone. Importantly, C6-curcumin liposomes were found to be less toxic on untransformed primary human cells (human mesenchymal stem cells) in comparison to OS cell lines. In addition, cell cycle assays on a KHOS cell line after treatment revealed that curcumin only liposomes induced G2/M arrest by upregulation of cyclin B1, while C6 only liposomes induced G1 arrest by downregulation of cyclin D1. C6-curcumin liposomes induced G2/M arrest and showed a combined effect in the expression levels of cyclin D1 and cyclin B1. The efficiency of the preparations was tested in vivo using a human osteosarcoma xenograft assay. Using pegylated liposomes to increase the plasma half-life and tagging with folate (FA) for targeted delivery in vivo, a significant reduction in tumor size was observed with C6-curcumin-FA liposomes. The encapsulation of two water insoluble drugs, curcumin and C6, in the lipid bilayer of liposomes enhances the cytotoxic effect and validates the potential of combined drug therapy. PMID:24380633
Effects of triglycerides on the hydrophobic drug loading capacity of saturated phosphatidylcholine-based liposomes.
Hong, Soon-Seok; Kim, So Hee; Lim, Soo-Jeong
A high drug-loading capacity is a critical factor for the clinical development of liposomal formulations. The accommodation of hydrophobic drugs within the liposomal membrane is often limited in saturated phosphatidylcholine (PC)-based liposomes owing to the rigidity of the lipid acyl chain. In the current study, we explored the possibility of improving the hydrophobic drug loading capacity of liposomes by incorporating triglyceride into liposomal membranes. Incorporation of Captex 300, a medium chain triglyceride, into liposomes composed of dimyristoylphosphatidylcholine and cholesterol greatly increased the fluidity and lamellarity of the resultant liposomes. Liposomal incorporation of medium or long chain, but not short chain, triglycerides greatly enhanced the concentration of loaded paclitaxel (PTX) in saturated PC-based liposomes. The enhancing effect of triglyceride saturated at a triglyceride content corresponding to the amount required to fluidize the liposome structure. In addition, the enhancing effect was not observed in unsaturated PC-based liposomes and was not associated with the solubility of PTX in each triglyceride. Triglycerides also enhanced the loading of docetaxel, another hydrophobic drug. Taken together, our results suggest that triglyceride incorporation in saturated PC-based liposomes provide an improved dosage form that enables increased hydrophobic drug loading by altering the fluidity and structure of liposomal membranes. PMID:25667981
Encapsulation of doxorubicin in liposomes containing phosphatidylethanol. Part 2: Physicochemical characterization and antitumor activity of "solid" liposomes
S. V. Babitskaya; A. P. Vlasov; V. I. Dolgopalets; M. V. Zhukova; M. A. Kisel'; B. B. Kuz'mitskii; A. E. Mashkovich; V. M. Nasek; O. V. Romanenko; V. M. Shnigir
Doxorubicin has been encapsulated into "solid" liposomes composed of a mixture of distearoyl analogs of phosphatidylcholine\\u000a and phosphatidylethanol (in a 3: 2 molar ratio). The liposomes are sterically stabilized by incorporating a conjugate of dipalmitoylphosphatidylethanolamine\\u000a with poly(ethylene glycol)-2000 in an amount of 5 wt % with respect to the total lipid content. The data of differential scanning\\u000a microcalorimetry method show
Photophysical properties of a new water soluble tetra thiamine substituted zinc phthalocyanine conjugated to gold nanorods of different aspect ratios.
Mthethwa, Thandekile; Antunes, Edith; Nyokong, Tebello
A water soluble zinc phthalocyanine substituted with thiamine is reported in this work. The aggregation of this compound in aqueous solutions causes quenching of the fluorescence quantum yields. Gold nanospheres and nanorods were linked to the phthalocyanine. X-ray photoelectron spectroscopy showed that both the amine and the sulphur groups on the thiamine substituent of the zinc phthalocyanine were involved in the linking to gold nanoparticles. The Pc showed an increase in the fluorescence quantum yields in the presence of the nanoparticles. The singlet oxygen quantum yield increased when the Pc was conjugated to the nanoparticles and even higher for larger aspect ratio gold nanorods. PMID:24671409
Tablets of pre-liposomes govern in situ formation of liposomes: concept and potential of the novel drug delivery system.
Vani?, Željka; Planinšek, Odon; Škalko-Basnet, Nataša; Tho, Ingunn
The purpose of this study was to develop a novel drug delivery system for challenging drugs with potential for scale-up manufacturing and controlled release of incorporated drug. Pre-liposomes powder containing metronidazole, lecithin and mannitol, prepared by spray-drying, was mixed with different tableting excipients (microcrystalline cellulose, lactose monohydrate, mannitol, dibasic calcium phosphate, pregelatinized starch, pectin or chitosan) and compressed into tablets. The delivery system was characterized with respect to (i) dry powder characteristics, (ii) mechanical tablet properties and drug release, and (iii) liposomal characteristics. The pre-liposomes powder was free-flowing, and tablets of similarly high qualities as tablets made of physical mixtures were prepared with all excipients. Liposomes were formed in situ upon tablet disintegration, dissolution or erosion depending on the type of tablet excipient used. The liposomal characteristics and drug release were found to depend on the tablet excipient. The new delivery system offers a unique synergy between the ability of liposomes to encapsulate and protect drugs and increased stability provided by compressed formulations. It can be adjusted for drug administration via various routes, e.g. oral, buccal and vaginal. PMID:24929211
The Photodynamic Antibacterial Effects of Silicon Phthalocyanine (Pc) 4
Dimaano, Matthew L.; Rozario, Chantal; Nerandzic, Michelle M.; Donskey, Curtis J.; Lam, Minh; Baron, Elma D.
The emergence of antibiotic-resistant strains in facultative anaerobic Gram-positive coccal bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), is a global health issue. Typically, MRSA strains are found associated with institutions like hospitals but recent data suggest that they are becoming more prevalent in community-acquired infections. It is thought that the incidence and prevalence of bacterial infections will continue to increase as (a) more frequent use of broad-spectrum antibiotics and immunosuppressive medications; (b) increased number of invasive medical procedures; and (c) higher incidence of neutropenia and HIV infections. Therefore, more optimal treatments, such as photodynamic therapy (PDT), are warranted. PDT requires the interaction of light, a photosensitizing agent, and molecular oxygen to induce cytotoxic effects. In this study, we investigated the efficacy and characterized the mechanism of cytotoxicity induced by photodynamic therapy sensitized by silicon phthalocyanine (Pc) 4 on (a) methicillin-sensitive Staphylococcus aureus (MSSA) (ATCC 25923); (b) community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) (ATCC 43300); and (c) hospital acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) (PFGE type 300). Our data include confocal image analysis, which confirmed that Pc 4 is taken up by all S. aureus strains, and viable cell recovery assay, which showed that concentrations as low as 1.0 ?M Pc 4 incubated for 3 h at 37 °C followed by light at 2.0 J/cm2 can reduce cell survival by 2–5 logs. These results are encouraging, but before PDT can be utilized as an alternative treatment for eradicating resistant strains, we must first characterize the mechanism of cell death that Pc 4-based PDT employs in eliminating these pathogens. PMID:25856680
The photodynamic antibacterial effects of silicon phthalocyanine (Pc) 4.
Dimaano, Matthew L; Rozario, Chantal; Nerandzic, Michelle M; Donskey, Curtis J; Lam, Minh; Baron, Elma D
The emergence of antibiotic-resistant strains in facultative anaerobic Gram-positive coccal bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), is a global health issue. Typically, MRSA strains are found associated with institutions like hospitals but recent data suggest that they are becoming more prevalent in community-acquired infections. It is thought that the incidence and prevalence of bacterial infections will continue to increase as (a) more frequent use of broad-spectrum antibiotics and immunosuppressive medications; (b) increased number of invasive medical procedures; and (c) higher incidence of neutropenia and HIV infections. Therefore, more optimal treatments, such as photodynamic therapy (PDT), are warranted. PDT requires the interaction of light, a photosensitizing agent, and molecular oxygen to induce cytotoxic effects. In this study, we investigated the efficacy and characterized the mechanism of cytotoxicity induced by photodynamic therapy sensitized by silicon phthalocyanine (Pc) 4 on (a) methicillin-sensitive Staphylococcus aureus (MSSA) (ATCC 25923); (b) community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) (ATCC 43300); and (c) hospital acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) (PFGE type 300). Our data include confocal image analysis, which confirmed that Pc 4 is taken up by all S. aureus strains, and viable cell recovery assay, which showed that concentrations as low as 1.0 ?M Pc 4 incubated for 3 h at 37 °C followed by light at 2.0 J/cm2 can reduce cell survival by 2-5 logs. These results are encouraging, but before PDT can be utilized as an alternative treatment for eradicating resistant strains, we must first characterize the mechanism of cell death that Pc 4-based PDT employs in eliminating these pathogens. PMID:25856680
Phthalocyanine-labeled LDL for tumor imaging and photodynamic therapy
NASA Astrophysics Data System (ADS)
Li, Hui; Marotta, Diane; Kim, Soungkyoo; Chance, Britton; Glickson, Jerry D.; Busch, Theresa M.; Zheng, Gang
Current limitation of both near-infrared (NIR) tumor imaging and photodynamic therapy (PDT) is their lack of sufficient tumor-to-tissue contrast due to the relatively non-specific nature of delivering dye to the tumor, which has led to false negatives for NIR imaging and inadequate therapeutic ratio for PDT. Hence, agents targeting "cancer signatures", i.e. molecules that accumulate selectively in cancer cells, are particular attractive. One of these signatures is low-density-lipoprotein receptor (LDLR), which is overexpressed in many tumors. We have developed pyropheophorbide cholesterol oleate reconstituted LDL as a LDLR-targeting photosensitizer (PS) and demonstrated its LDLR-mediated uptake in vitro and in vivo. To improve the labeling efficiency for achieving high probe/protein ratio, tetra-t-butyl silicon phthalocyanine bearing two oleate moieties at its axial positions, (tBu)4SiPcBOA, was designed and synthesized. This compound was designed to 1) prevent the PS aggregation; 2) improve the PS solubility in non-polar solvent; and 3) maximize the PS binding to LDL phospholipid monolayer. Using this novel strategy, (tBu)4SiPcBOA was reconstituted into LDL (r-SiPcBOA-LDL) with a very high payload (500:1 molar ratio). In addition, (tBu)4SiPcBOA reconstituted acetylated LDL (r-SiPcBOA)-AcLDL with similar payload was also prepared. Since Ac-LDL cannot bind to LDLR, (r-SiPcBOA)-AcLDL can serve as the negative control to evaluate LDLR targeting specificity. For biological evaluation of these new agents, confocal microscopy and in vitro PDT protocols were performed using LDLR-overexpressing human hepatoblastoma G2 (HepG2) tumor model. These studies suggest that LDL serves as a delivery vehicle to bring large amount of the NIR/PDT agents selectively to tumor cells overexpressing LDLR.
Ambient induced degradation and chemically activated recovery in copper phthalocyanine thin film transistors
Kummel, Andrew C.
morphology of the pentacene films dra- matically influenced the effects of the atmospheric contami- nants based OTFTs.15 Metal phthalocyanines MPcs are another well studied group of organic semiconductors layer.6,17,18 A systematic approach to iso- lating the cause of device degradation "aging" in copper
Hybrid solar cells based on porous Si and copper phthalocyanine derivatives
Euler, William B.
and inorganic materials. For purely organic solar cells, the use of donor acceptor molecules,13 polymers,4Hybrid solar cells based on porous Si and copper phthalocyanine derivatives I. A. Levitskya 25 October 2004) We demonstrate a solar cell based on n-type nanoporous Si (PSi) filled with copper
Atomic Imaging of the Irreversible Sensing Mechanism of NO2 Adsorption on Copper Phthalocyanine
Kummel, Andrew C.
(II) phthalocyanine (CuPc) monolayers is observed using ultrahigh vacuum (UHV) scanning tunneling microscopy (STM vapor deposition, spin coating, and spray coating. While other organic thin films may have higher, in a simplified model, act as "dopants":18,19 Pure MPc films are insulating in vacuum, but they become p
Interaction of cationic phthalocyanines with DNA. Importance of the structure of the substituents.
López Zeballos, N C; Gauna, G A; García Vior, M C; Awruch, J; Dicelio, L E
The interaction of novel zinc (II) cationic phthalocyanines with CT-DNA was studied using absorption and fluorescence spectroscopy, as well as thermal denaturation profiles. Results showed an electrostatic interaction between the phthalocyanines and CT-DNA. The properties of these phthalocyanines were compared taking the structure of the macrocycle peripheral substituents into account. 2,9(10),16(17),23(24)-tetrakis[(N-butyl-N-methylammonium)ethylsulfanyl]phthalocyaninatozinc(II) tetraiodide (Pc6) had a greater affinity for the CT-DNA helix than its bioisoster 2,9(10),16(17),23(24)-tetrakis[(N-dibutyl-N-methylammonium)ethoxy]phthalocyaninatozinc(II) tetraiodide (Pc7). 2,9(10),16(17),23(24)-tetrakis[(2-trimethylammonium)ethyl-sulfanyl]phthalocyaninatozinc(II) tetraiodide (Pc13) also carried a sulfur atom like Pc6, but linked to bulky substituents such as trimethylammonium groups. The planar aromatic region of the cationic phthalocyanines in this study appears to be unable to facilitate their intercalation with CT-DNA. PMID:24838031
A preliminary study of the manufacture of phthalocyanine dyes and pigments was conducted to determine if process waste streams might contain hazardous material. The study first identifies the dyes and pigments that belong to this segment of the industry, the amounts produced, and...
Molecular Interactions Between Alcohols and Metal Phthalocyanine Thin Films for Optical Gas Sensor Applications
NASA Astrophysics Data System (ADS)
Uttiya, Sureeporn; Kladsomboon, Sumana; Chamlek, Onanong; Suwannet, Wiriya; Osotchan, Tanakorn; Kerdcharoen, Teerakiat; Brinkmann, Martin; Pratontep, Sirapat
Optically active organic gas sensors represent a promising molecular sensing device with low power consumption. We report experimental and computational investigations into the molecular interactions of metal phthalocyanine thin films with alcohol vapor. In the gas-sensing regime, the interactions of zinc phthalocyanine and alcohol molecules were studied by the Density Functional Theory (DFT) calculations, in comparison to the x-ray absorption spectroscopy. The DFT results reveal a reversible charge interaction mechanism between the zinc atom and the oxygen atom in the alcohol OH group, which corresponds to a shift in the x-ray absorption edge of the zinc atom. In the irreversible interaction regime, the effect of saturated alcohol vapor on spin-coated zinc phthalocyanine films was studied by the phase contrast microscopy, the optical absorption spectroscopy, and the transmission electron microscopy. Annealing the spin-coated films in saturated methanol vapor was found to induce an irreversible structural transformation from an amorphous to a crystalline phase, similar to the effect of a thermal annealing process. These crystallization processes of the zinc phthalocyanine films were also found to enhance their stability and alcohol sensing performance.
Gas Sensing Mechanism in Chemiresistive Cobalt and Metal-Free Phthalocyanine Thin Films
Kummel, Andrew C.
/phthalocyanine interface leads to the formation of oxidized MPc+ and O2 - species and injection of hole charge carriers that the formation of charge-transfer complexes by coordination of O2 to MPc metal centers at the air by weak hydrophobic and possibly charge-transfer interactions.
Schottky barrier formation and transport properties in copper phthalocyanine dispersed in polycarbonate
Tharwat G. Abdel-Malik
The electrical and photoelectrical properties of photovoltaic cells, made by dispersing particles of copper phthalocyanine (CuPc) in a binder polymer (polycarbonate MK) and sandwiching between gold nad indium electrodes, have been studied. A complete study of the current as a function of voltage and temperature is carried out. At low voltages, the current in the forward direction varies exponentially with
THE JOURNAL OF CHEMICAL PHYSICS 133, 214703 (2010) Copper-phthalocyanine based metalorganic interfaces: The effect
Ortega, Enrique
THE JOURNAL OF CHEMICAL PHYSICS 133, 214703 (2010) Copper-phthalocyanine based metal, Universidad del Pais Vasco, Pza. Ońate 2, 20018 San Sebastián, Spain 4 Nano-Bio Spectroscopy Group and ETSF; accepted 12 October 2010; published online 3 December 2010) Metalorganic interfaces based on copper
The surface reaction and diffusion of NO 2 in lead phthalocyanine thin film
Y. H. Ju; C. Hsieh; C. J. Liu
The responses of lead phthalocyanine thin films upon encountering of NO2 gas were studied both experimentally and theoretically. A surface adsorption\\/desorption and bulk diffusion mechanism was proposed to describe the response. Laplace transform was employed to solve the resulting diffusion equation and an analytical solution was obtained. The analytical results show that the steady state current depends on parameters such
ELSEVIER Synthetic ~Metals 84 (1997) 733-734 Electrical transport in monolayers of phthalocyanine molecular wires
Dekker, Cees
ELSEVIER Synthetic ~Metals 84 (1997) 733-734 Electrical transport in monolayers of phthalocyanine for electrical transport studies on single molecular wires. Current-voltage measurements on monolayers of a single molecular wire bridging two closely spaced electrodes. Keywords: electrical transport measurements
Fabrication and characterization of organic solar cells using metal complex of phthalocyanines
NASA Astrophysics Data System (ADS)
Kida, Tomoyasu; Suzuki, Atsushi; Akiyama, Tsuyoshi; Oku, Takeo
Fabrication and characterization of organic solar cells using shuttle-cock-type phthalocyanines were carried out. Photovoltaic properties of the solar cells with inverted structures were investigated by current density-voltage characteristics. Effects of phase transition between H and J aggregates on the photovoltaic and optical properties were investigated. The photovoltaic mechanisms, energy levels and band gap of active layers were discussed.
Metal (2) 4,4',4",4'" phthalocyanine tetraamines as curing agents for epoxy resins
NASA Technical Reports Server (NTRS)
Achar, B. N.; Fohlen, G. M.; Parker, J. A. (inventors)
Metal, preferably divalent copper, cobalt or nickel, phthalocyanine tetraamines are used as curing agents for epoxides. The resulting copolymers have high thermal and chemical resistance and are homogeneous. They are useful as binders for laminates, e.g., graphite cloth laminate.
Ab initio theoretical investigation of Phthalocyanine-Semiconductor hybrid systems. G. Mattioli,1, 2
Giannozzi, Paolo
as dye-sensitizers for hybrid organic-inorganic so- lar cells1,11 . · Transition metals with d electrons-surface interaction in hybrid systems formed by phthalocyanines (Pcs) and inorganic semiconductors (IS) has been effectively coupled Pcs-IS systems, assumed here to be characterized by the formation of chemical bonds
Spectroscopic fingerprints of work-function-controlled phthalocyanine charging on metal surfaces.
Borghetti, Patrizia; El-Sayed, Afaf; Goiri, Elizabeth; Rogero, Celia; Lobo-Checa, Jorge; Floreano, Luca; Ortega, Jose Enrique; de Oteyza, Dimas G
The electronic character of a ?-conjugated molecular overlayer on a metal surface can change from semiconducting to metallic, depending on how molecular orbitals arrange with respect to the electrode's Fermi level. Molecular level alignment is thus a key property that strongly influences the performance of organic-based devices. In this work, we report how the electronic level alignment of copper phthalocyanines on metal surfaces can be tailored by controlling the substrate work function. We even show the way to finely tune it for one fixed phthalocyanine-metal combination without the need to intercalate substrate-functionalizing buffer layers. Instead, the work function is trimmed by appropriate design of the phthalocyanine's supramolecular environment, such that charge transfer into empty molecular levels can be triggered across the metal-organic interface. These intriguing observations are the outcome of a powerful combination of surface-sensitive electron spectroscopies, which further reveal a number of characteristic spectroscopic fingerprints of a lifted LUMO degeneracy associated with the partial phthalocyanine charging. PMID:25426520
Etoposide Incorporated into Camel Milk Phospholipids Liposomes Shows Increased Activity against Fibrosarcoma in a Mouse Model
Maswadeh, Hamzah M.; Aljarbou, Ahmad N.; Alorainy, Mohammed S.; Alsharidah, Mansour S.; Khan, Masood A.
Phospholipids were isolated from camel milk and identified by using high performance liquid chromatography and gas chromatography-mass spectrometry (GC/MS). Anticancer drug etoposide (ETP) was entrapped in liposomes, prepared from camel milk phospholipids, to determine its activity against fibrosarcoma in a murine model. Fibrosarcoma was induced in mice by injecting benzopyrene (BAP) and tumor-bearing mice were treated with various formulations of etoposide, including etoposide entrapped camel milk phospholipids liposomes (ETP-Cam-liposomes) and etoposide-loaded DPPC-liposomes (ETP-DPPC-liposomes). The tumor-bearing mice treated with ETP-Cam-liposomes showed slow progression of tumors and increased survival compared to free ETP or ETP-DPPC-liposomes. These results suggest that ETP-Cam-liposomes may prove to be a better drug delivery system for anticancer drugs. PMID:25821817
Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy
Chang, Hsin-I; Yeh, Ming-Kung
Research on liposome formulations has progressed from that on conventional vesicles to new generation liposomes, such as cationic liposomes, temperature sensitive liposomes, and virosomes, by modulating the formulation techniques and lipid composition. Many research papers focus on the correlation of blood circulation time and drug accumulation in target tissues with physicochemical properties of liposomal formulations, including particle size, membrane lamellarity, surface charge, permeability, encapsulation volume, shelf time, and release rate. This review is mainly to compare the therapeutic effect of current clinically approved liposome-based drugs with free drugs, and to also determine the clinical effect via liposomal variations in lipid composition. Furthermore, the major preclinical and clinical data related to the principal liposomal formulations are also summarized. PMID:22275822
Liposomal diltiazem HCl as ocular drug delivery system for glaucoma.
Mokhtar Ibrahim, Mahmoud; Tawfique, Salma A H; Mahdy, Mahmoud M
In this study, unilamellar liposomal vesicles of diltiazem HCl (DH) were prepared using either reversed phase evaporation (REV) or proliposome methods. Soya phosphatidylcholine (SPC) was used for preparing the liposomes, and the vesicles were rigidified using cholesterol (Chol) or cetyl alcohol (CA) in different molarities. The major differences in both the entrapment efficiency percent (EE%) and drug release were evaluated as a function of the method of preparation, Chol or CA contents, and charging lipids. Moreover, the morphology of the vesicles was confirmed by transmission electron microscopy. The effects of Chol or CA incorporation into the liposomes were discussed based on thermal analysis. The in vivo evaluation of liposomal DH was assessed using intra-ocular pressure (IOP), reducing effects in rabbit eyes. Liposomes prepared via REV exhibited higher EE% and lower release rates when compared with those prepared from proliposomes. The incorporation of either Chol or CA in the liposomes enhanced the EE% and decreased the release rates; however, Chol yielded higher results than CA. In addition, both dicetyl phosphate (DCP; negative charge inducer) and stearyl amine (SA, positive charge inducer) decreased the EE% and increased the DH release rate. The in vivo antiglaucoma effects of the liposomes were calculated according to the area above the IOP/Time curve, the maximum response and the time for the maximum response and were compared with effects of the DH solution. The results were in the following order: DH solution?
Targeting Stealth liposomes in a murine model of human small cell lung cancer
Joăo N. Moreira; Rogério Gaspar; Theresa M. Allen
Tumor accumulation and therapeutic activity of Stealth liposomes loaded with doxorubicin (DXR) were examined in Balb\\/c nude mice xenografts inoculated subcutaneously with the human small cell lung cancer (SCLC) cell line, H69. Mice were treated with non-targeted liposomes (SL) or liposomes targeted with antagonist G coupled to the liposome surface (SLG). SLG showed 30–44-fold higher binding to H69 cells harvested
Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice1
Zheng-hong WU; Qi-neng PING; Yi WEI; Jia-ming LAI
AIM: To evaluate the hypoglycemic efficacy of insulin liposomes coated by chitosan with different molecular weights and concentrations after oral administration in mice. METHODS: Insulin-liposomes were prepared by reversed-phase evaporation. Chitosan coating was carried out by incubation of the liposomal suspensions with the chitosan solution. The hypoglycemic efficacies of chitosan-coated insulin liposomes were investigated by monitor- ing the blood glucose
Effect of liposomalization on the antitumor activity, side-effects and tissue distribution of CPT11
Yasuyuki Sadzuka; Sachiyo Hirotsu; Sadao Hirota
We have examined the efficacy of liposomalization and polyethyleneglycol (PEG) modification of liposomes on the antitumor activity, side-effects and tissue distribution of irinotecan hydrochloride (CPT-11). PEG-liposome was confirmed to elevate the plasma circulation of CPT-11 and SN-38 (active metabolite) concentrations. The tumor accumulation of CPT-11 and SN-38 was increased by the PEG-modified liposomes. The antitumor activity of CPT-11 increased due
Cellular fusion and whitening effect of a chitosan derivative coated liposome
Yang-Wei Wang; Chi-Hsiung Jou; Chia-Chun Hung; Ming-Chien Yang
In this study, a derivative of chitosan, N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC), was coated onto the liposomes made of cholesterol and 1,2-palmitoyl-sn-glycero-3-phosphatidylcholine (DPPC). These coated liposomes were loaded with kojic acid for skin whitening. The appearance of liposome was examined using transmission electron microscope (TEM), and the coating of HTCC to the liposome was confirmed by infrared spectroscopy. By
Targeting liposomes with protein drugs to the blood–brain barrier in vitro
Corine C. Visser; Sanja Stevanovi?; L. Heleen Voorwinden; Louis van Bloois; Pieter J. Gaillard; Meindert Danhof; Daan J. A. Crommelin; Albertus G. de Boer
In this study, we aim to target pegylated liposomes loaded with horseradish peroxidase (HRP) and tagged with transferrin (Tf) to the BBB in vitro. Liposomes were prepared with the post-insertion technique: micelles of polyethylene glycol (PEG) and PEG-Tf were inserted into pre-formed liposomes containing HRP. Tf was measured indirectly by measuring iron via atomic absorption spectroscopy. All liposomes were around
Evaluation of circulation profiles of liposomes coated with hydrophilic polymers having different molecular weights in rats
Hirofumi Takeuchi; Hiroyuki Kojima; Hiromitsu Yamamoto; Yoshiaki Kawashima
The purpose of this study was to evaluate the circulating properties of liposomes coated with modified polyvinyl alcohol (PVA-R) having different molecular weights (6000, 9000 and 20?000). The size controlled liposomes (egg phosphatidylcholine (or distearoylphosphatidylcholine):cholesterol=7:3 in a molar ratio) were prepared by the hydration method followed by sonication. Polymer coated liposomes were prepared by just mixing the resultant liposomal suspension
Enhanced localization of anticancer drug in tumor tissue using polyethylenimine-conjugated cationic liposomes
NASA Astrophysics Data System (ADS)
Han, Hee Dong; Byeon, Yeongseon; Jeon, Hat Nim; Shin, Byung Cheol
Liposome-based drug delivery systems hold great potential for cancer therapy. However, to enhance the localization of payloads, an efficient method of systemic delivery of liposomes to tumor tissues is required. In this study, we developed cationic liposomes composed of polyethylenimine (PEI)-conjugated distearoylglycerophosphoethanolamine (DSPE) as an enhanced local drug delivery system. The particle size of DSPE-PEI liposomes was 130 ± 10 nm and the zeta potential of liposomes was increased from -25 to 30 mV by the incorporation of cationic PEI onto the liposomal membrane. Intracellular uptake of DSPE-PEI liposomes by tumor cells was 14-fold higher than that of DSPE liposomes. After intratumoral injection of liposomes into tumor-bearing mice, DSPE-PEI liposomes showed higher and sustained localization in tumor tissue compared to DSPE liposomes. Taken together, our findings suggest that DSPE-PEI liposomes have the potential to be used as effective drug carriers for enhanced intracellular uptake and localization of anticancer drugs in tumor tissue through intratumoral injection.
Preparation of Calcium-Loaded Liposomes and Their Use in Calcium Phosphate Formation
Preparation of Calcium-Loaded Liposomes and Their Use in Calcium Phosphate Formation Phillip B within dipalmitoylphosphatidylcholine lipid vesicles, which were then used to form calcium phosphate as high as 85 mM. Addition of inorganic phosphate to the calcium-loaded liposomes resulted in liposome
Curcumin-loaded ?-cyclodextrin liposomal nanoparticles as delivery vehicles for osteosarcoma
Santosh S. Dhule; Patrice Penfornis; Trivia Frazier; Ryan Walker; Joshua Feldman; Grace Tan; Jibao He; Alina Alb; Vijay John; Radhika Pochampally
The delivery of curcumin, a broad-spectrum anticancer drug, has been explored in the form of liposomal nanoparticles to treat osteosarcoma (OS). Curcumin is water insoluble and an effective delivery route is through encapsulation in cyclodextrins followed by a second encapsulation in liposomes. Liposomal curcumin's potential was evaluated against cancer models of mesenchymal (OS) and epithelial origin (breast cancer). The resulting
Drainage of Fluorescent Liposomes from the Vitreous to Cervical Lymph Nodes via Conjunctival Lymphatics
S. Camelo; L. Lajavardi; A. Bochot; B. Goldenberg; M. C. Naud; E. Fattal; F. Behar-Cohen; Y. de Kozak
The use of liposomes as carriers for the delivery of biologically active molecules into the eye is of major interest. Indeed, encapsulation of biologically active molecules in liposomes may increase their bioavailability and may induce a sustained release, thus avoiding repeated intraocular injections and reducing side effects. We describe here the fate of rhodamine-conjugated liposomes (Rh-Lip) injected into the vitreous
Improved permeability of acyclovir: optimization of mucoadhesive liposomes using the phospholipid vesicle-based permeation assay.
Naderkhani, Elenaz; Erber, Astrid; Škalko-Basnet, Nataša; Flaten, Gřril Eide
The antiviral drug acyclovir (ACV) suffers from poor solubility both in lipophilic and hydrophilic environment, leading to low and highly variable bioavailability. To overcome these limitations, this study aimed at designing mucoadhesive ACV-containing liposomes to improve its permeability. Liposomes were prepared from egg phosphatidylcholine (E-PC) and E-PC/egg phosphatidylglycerol (E-PC/E-PG) and their surfaces coated with Carbopol. All liposomal formulations were fully characterized and for the first time the phospholipid vesicle-based permeation assay (PVPA) was used for testing in vitro permeability of drug from mucoadhesive liposome formulations. The negatively charged E-PC/E-PG liposomes could encapsulate more ACV than neutral E-PC liposomes. Coating with Carbopol increased the entrapment in the neutral E-PC liposomes. The incorporation of ACV into liposomes exhibited significant increase in its in vitro permeability, compared with its aqueous solution. The neutral E-PC liposomal formulations exhibited higher ACV permeability values compared with charged E-PC/E-PG formulations. Coating with Carbopol significantly enhanced the permeability from the E-PC/E-PG liposomes, as well as sonicated E-PC liposomes, which showed the highest permeability of all tested formulations. The increased permeability was according to the formulations' mucoadhesive properties. This indicates that the PVPA is suitable to distinguish between permeability of ACV from different mucoadhesive liposome formulations developed for various routes of administration. PMID:24395733
Is control of distribution of liposomes between tumors and bone marrow possible?
Atsushi Nagayasu; Kazuko Uchiyama; Tomoyo Nishida; Yumiko Yamagiwa; Yumiko Kawai; Hiroshi Kiwada
The objective of this study is to clarify to what extent the accumulation of liposomes from the blood into the tumor and bone marrow can be controlled by liposome size and membrane fluidity. Liposomes with different diameters (50–400 nm) and different membrane fluidity were prepared from hydrogenated egg phosphatidylcholine (HEPC) or egg phosphatidylcholine (EPC), cholesterol (Ch) and dicetylphosphate in various
Effect of formulation design and freeze-drying on properties of fluconazole multilamellar liposomes
El-Nesr, Ola H.; Yahiya, Soad A.; El-Gazayerly, Omaima N.
Fluconazole-entrapped multilamellar liposomes were prepared using the thin-film hydration method. The effects of cholesterol molar ratio, charge-inducing agents, and ?-tocopherol acetate on encapsulation efficiency values and in vitro drug release of multilamellar liposomes were studied. Freeze-dried liposomal products were prepared with or without cryoprotectants. Results showed that incorporation of stearylamine resulted in an increased entrapment of fluconazole, whereas incorporation of dicetyl phosphate decreased the drug entrapment efficiency. The incorporation of ?-tocopherol acetate into fluconazole multilamellar liposomes resulted in the increase of entrapment efficiency of fluconazole liposomes. In vitro release studies revealed that incorporation of cholesterol into multilamellar liposomal formulations decreased drug permeability from formulations. Positively charged fluconazole multilamellar liposomes gave rise to a slow release rate compared to neutral liposomes whereas negatively charged fluconazole liposomes showed a rapid release rate. Physical stability studies showed that lyophilized cake of liposomes without cryoprotectants was compact and difficult to reconstitute compared to fluffy easily reconstituted cakes upon using cryoprotectants. Fluconazole retained in freeze-dried liposomes without cryoprotectants was 63.452% compared to 91.877% using three grams of trehalose as a cryoprotectant per gram lipid in positively charged multilamellar liposomes. Physical stability studies showed superior potentials of the lyophilized product after reconstitution in comparison with those of a solution product. PMID:23960730
Cationic Charge Determines the Distribution of Liposomes between the Vascular and Extravascular Compartments of Tumors1
Robert B. Campbell; Dai Fukumura; Edward B. Brown; Laureen M. Mazzola; Yotaro Izumi; Rakesh K. Jain; Vladimir P. Torchilin; Lance L. Munn
Tumor vessels possess unique physiological features that might be exploited for improving drug delivery. In the present study, we investigate the possibility of modifying polyethylene glycol-ylated liposome cationic charge of polyethylene glycol coated liposomes to optimize delivery to tumor vessels using biodistribution studies and intravital microscopy. The majority of liposomes accumulated in the liver, and increasing charge resulted in lower
Effect of formulation design and freeze-drying on properties of fluconazole multilamellar liposomes.
El-Nesr, Ola H; Yahiya, Soad A; El-Gazayerly, Omaima N
Fluconazole-entrapped multilamellar liposomes were prepared using the thin-film hydration method. The effects of cholesterol molar ratio, charge-inducing agents, and ?-tocopherol acetate on encapsulation efficiency values and in vitro drug release of multilamellar liposomes were studied. Freeze-dried liposomal products were prepared with or without cryoprotectants. Results showed that incorporation of stearylamine resulted in an increased entrapment of fluconazole, whereas incorporation of dicetyl phosphate decreased the drug entrapment efficiency. The incorporation of ?-tocopherol acetate into fluconazole multilamellar liposomes resulted in the increase of entrapment efficiency of fluconazole liposomes. In vitro release studies revealed that incorporation of cholesterol into multilamellar liposomal formulations decreased drug permeability from formulations. Positively charged fluconazole multilamellar liposomes gave rise to a slow release rate compared to neutral liposomes whereas negatively charged fluconazole liposomes showed a rapid release rate. Physical stability studies showed that lyophilized cake of liposomes without cryoprotectants was compact and difficult to reconstitute compared to fluffy easily reconstituted cakes upon using cryoprotectants. Fluconazole retained in freeze-dried liposomes without cryoprotectants was 63.452% compared to 91.877% using three grams of trehalose as a cryoprotectant per gram lipid in positively charged multilamellar liposomes. Physical stability studies showed superior potentials of the lyophilized product after reconstitution in comparison with those of a solution product. PMID:23960730
Interactions of liposome carriers with infectious fungal hyphae reveals the role of ?-glucans.
Chavan, Neelam L; Young, Joseph K; Drezek, Rebekah A; Lewis, Russell; Bikram, Malavosklish
Relatively little is known about how liposomal formulations modulate drug delivery to fungal pathogens. We compared patterns of hyphal cell wall binding for empty rhodmine-labeled liposomes and the clinically available amphotericin B-containing liposomal formulation (AmBisome) in Aspergillus fumigatus and Candida albicans. Following 0.5 h of coincubation with A. fumigatus , empty liposomes concentrated primarily in fungal septae along at the surface of the cell wall, suggesting that liposome uptake is concentrated in areas of the cell wall where linear glucan is exposed on the cell surface, which was confirmed by aniline blue staining. Consistent with this hypothesis, pretreatment of liposomes with soluble linear glucan (laminarin) decreased liposome binding in both Aspergillus and Candida fungal hyphae, while growth of Aspergillus hyphae in the presence of an agent that increases fungal cell wall surface exposure of linear ?-glucans without cell death (caspofungin) increased liposome uptake throughout the Aspergillus fungal cell wall. Increasing the polyethylene glycol (PEG) concentration in liposomes from 0 to 30% significantly increased fungal uptake of liposomes that was only modestly attenuated when fungal cells were incubated in serum concentrations ranging from 10 to 100%. The presence of ?-glucans on the fungal hyphae cell walls of Aspergillus fumigatus is one of the factors responsible for mediating the binding of liposome carriers to the hyphae and could explain possible synergy reported between liposomal amphotericin B and echinocanins. PMID:22770505
Investigations of a new, highly negative liposome with improved biodistribution for imaging
Hnatowich, D.J.; Clancy, B.
An attractive feature of liposomes is the wide range of lipid composition that can lead to liposome formation, coupled with the observation that liposome biodistribution may be altered by varying lipid composition. For instance, adding charged lipids to neutral lecithin will alter the biodistribution of the resulting charged liposomes. We have prepared highly negative liposomes by replacing lecithin with negatively charged cardiolipin. The liposomes have been labeled in the lipid phase with Ga-67 and Tc-99m oxine and their properties evaluated. The expected high negative charge of the resulting liposomes was confirmed by an ion-exchange chromatographic technique. Using paper chromatography, the stability of the label was determined during incubation in saline and serum. Finally, biodistributions were determined at 2 h in mice, and the results compared with those for negative lecithin liposomes. Accumulated activities in liver and spleen were reduced by factors of five and 20, respectively, over lecithin liposomes. Since preferential accumulation of activity in these organs constitutes the biggest limitation to the use of lecithin liposomes, cardiolipin liposomes may prove to be more useful carriers of radioactivity in imaging applications. More importantly, however, these results illustrate the value of studying novel liposome types as potential radiopharmaceuticals.
Association of hydrophobically-modified poly(ethylene glycol) with fusogenic liposomes
Auguste, Debra T.
Association of hydrophobically-modified poly(ethylene glycol) with fusogenic liposomes Debra T interactions to shield liposomes by incorporating multiple hydrophobic anchoring sites on polyethylene glycol. Fusogenic liposomes prepared from N-C12-DOPE:DOPC 7:3 (mol:mol) were equilibrated with HMPEGs. Affinity
Effects of Counterions on Molecular Transport Across Liposome Bilayer: Probed by Second Harmonic Generation
Eisenthal, Kenneth B.
Effects of Counterions on Molecular Transport Across Liposome Bilayer: Probed by Second Harmonic) of the dioleoylphosphatidylglycerol (DOPG) liposome has been studied by the SHG technique. This is the first time to our knowledge mechanism is presented. 1. Introduction Liposomes have been widely used to investigate membrane functions
Curved FtsZ protofilaments generate bending forces on liposome membranes
Erickson, Harold P.
Curved FtsZ protofilaments generate bending forces on liposome membranes Masaki Osawa*, David E concave depres- sions, bending the membrane in the same direction as the Z ring inside liposomes is approximately 180 degrees from the C-terminal tether. When mts-FtsZ-YFP was applied to the outside of liposomes
Forster resonance energy transfer in liposomes: Measurements of transmembrane helix dimerization in the native
Wimley, William C.
Fo¨rster resonance energy transfer in liposomes: Measurements of transmembrane helix dimerization discuss Fo¨rster resonance energy transfer (FRET) in liposomes as a method to probe the dimerization in liposomes can be measured accurately provided that attention is paid to sample homogeneity and sample
Rupture of a liposomal vesicle Marco A. Idiart and Yan Levin
Levin, Yan
Rupture of a liposomal vesicle Marco A. Idiart and Yan Levin Instituto de Física, UFRGS, Caixa the liposomal size, internal solute concentration, and pore diameter is solved numerically. We find that dependent on the internal solute concentration and vesicle size, liposomes can stay pore free, nucleate
Anionic Saccharides Activate Liposomes Containing Phospholipids Bearing a Boronic Acid for
Smith, Bradley D.
Anionic Saccharides Activate Liposomes Containing Phospholipids Bearing a Boronic Acid for Ca2 Here we describe a functional mimic of that general scheme, where liposomes coated with a synthetic. Protons and divalent metal cations such as Ca2+ are often used to promote the fusion of liposomes
A liposome-based ion release impedance sensor for biological detection
Bashir, Rashid
A liposome-based ion release impedance sensor for biological detection Gregory L. Damhorst-on-a-chip strategy for biological detection based on liposome tagging and ion-release impedance spectroscopy. Ion-immobilized antigens. We demonstrate the quanti- fication of these liposomes by real-time impedance measure- ments
Sarcolipin, the Shorter Homologue of Phospholamban, Forms Oligomeric Structures in Detergent Micelles and in Liposomes*
Thomas, David D.
Micelles and in Liposomes* Received for publication, March 20, 2001, and in revised form, June 11, 2001-linking showed that also in liposomes SLN has the ability to self-associate to oli- gomers. PLB-(2452) specifically oligomerized to pentam- ers in the presence of octylpolyoxyethylene as well as in liposomes at low
Giant liposomes in physiological buffer using electroformation in a flow chamber
Mayer, Michael
Giant liposomes in physiological buffer using electroformation in a flow chamber Daniel J. Estes April 2005 Abstract We describe a method to obtain giant liposomes (diameter 10100 Am) in solutions electroformation on ITO electrodes, we formed surface-attached giant liposomes in solutions of glycerol in a flow
Enhanced cell binding using liposomes containing an artificial carbohydrate-binding receptor
Smith, Bradley D.
Enhanced cell binding using liposomes containing an artificial carbohydrate-binding receptor Yvonne) 7th October 1999, Accepted 1st December 1999 Liposomes containing phospholipids bearing a sugar liposomes that selectively self- assemble,1 or interact with specific cell-types,2 as this will likely lead
Thermosensitive Liposomes Modified with Poly(N-isopropylacrylamide-co-propylacrylic acid) Copolymers
Thermosensitive Liposomes Modified with Poly(N-isopropylacrylamide-co-propylacrylic acid liposome (pTSL) was developed for the delivery of Doxorubicin (DOX) for cancer therapy. Copolymers copolymers with dual pH/temperature-dependent phase transition properties. When attached to liposomes
Doxorubicin physical state in solution and inside liposomes loaded via a pH gradient
Gruner, Sol M.
Doxorubicin physical state in solution and inside liposomes loaded via a pH gradient Xingong Li R. Perkins aY * a The Liposome Company, Inc., One Research Way, Princeton, NJ 08540, USA b/cholesterol liposomes that were loaded via a transmembrane pH gradient. Using cryogenic electron microscopy (cryo-EM) we
Docking of Liposomes to Planar Surfaces Mediated by trans-SNARE Complexes
Texas at Austin. University of
Docking of Liposomes to Planar Surfaces Mediated by trans-SNARE Complexes Olga Vites,* Ernst here that liposomes containing synaptobrevin firmly attach to planar surfaces containing immobilized stability and is capable of substituting in liposome fusion assays. Vesicle attachment is initiated by SNARE
Time-Resolved Fluorescence Analysis of the Photosystem II Antenna Proteins in Detergent Micelles and Liposomes
and Liposomes Ismael Moya, Mariuccia Silvestri,§ Olivier Vallon,| Gianfelice Cinque, and Roberto Bassi*, LURE conformation of the Lhc proteins. Upon incorporation of Lhc proteins into liposomes, a quenching of chlorophyll in the liposomes, and therefore the probability of protein-protein interactions, a further decrease of fluorescence
Arabidopsis dynamin-related protein 1A polymers bind, but do not tubulate, liposomes
Bednarek, Sebastian Y.
Arabidopsis dynamin-related protein 1A polymers bind, but do not tubulate, liposomes Steven K Available online 18 February 2010 Keywords: Arabidopsis DRP1A Dynamin GTPase Liposome flotation Spotted staining electron micros- copy. These polymers interact with protein-free liposomes whose lipid composition
Films of Agarose Enable Rapid Formation of Giant Liposomes in Solutions of Physiologic Ionic Strength
Mayer, Michael
Films of Agarose Enable Rapid Formation of Giant Liposomes in Solutions of Physiologic Ionic: This paper describes a method to form giant liposomes in solutions of physiologic ionic strength, such as phosphate buffered saline (PBS) or 150 mM KCl. Formation of these cell-sized liposomes proceeded from hybrid
Rhodopsin self-associates in asolectin liposomes Steven E. Mansoor*, Krzysztof Palczewski
Palczewski, Krzysztof
Rhodopsin self-associates in asolectin liposomes Steven E. Mansoor*, Krzysztof Palczewski molecules reconstituted into asolectin liposomes. The low receptor density used in the measurements ensured) techniques to assess the apparent distance between Rh mole- cules reconstituted in asolectin liposomes at low
Biopolymer-Connected Liposome Networks as Injectable Biomaterials Capable of Sustained Local Drug Delivery
Raghavan, Srinivasa
Biopolymer-Connected Liposome Networks as Injectable Biomaterials Capable of Sustained Local Drug hydrophobic side-chains, such as hydrophobically modified chitosan (hmC), can connect liposomes into a gel network via hydrophobic interactions. In this paper, we show that such liposome gels possess an attractive
Microcalorimetric investigation of the interaction of polysorbate surfactants with unilamellar phosphatidylcholines liposomes
Li-Min Tasi; Der-Zen Liu; Wen-Yih Chen
The physical stability of liposome was discussed by the zeta potential and isothermal titration calorimetry (ITC) measurements. In our system, the liposomes containing egg-PC, ?-tocopherol and various quantities of polysorbate susfactants (Tween 20 and Tween 80) were prepared herein by the probe sonication method. The stability of these liposomes were also monitored and discussed by examining the size change with
Convection-enhanced delivery of liposomal doxorubicin in intracranial brain tumor xenografts
Yoji Yamashita; Ryuta Saito; Michal T. Krauze; Tomohiro Kawaguchi; Charles Noble; Daryl C. Drummond; Dmitri B. Kirpotin; John W. Park; Mitchel S. Berger; Krystof S. Bankiewicz
We previously reported that convection-enhanced delivery (CED) of liposomes into brain tissue and intracranial brain tumor xenografts produced robust tissue distribution that can be detected by magnetic resonance imaging. Considering image-guided CED of therapeutic liposomes as a promising strategy for the treatment of brain tumors, we evaluated the efficacy of pegylated liposomal doxorubicin delivered by CED in an animal model.
Evaluation of circulation profiles of liposomes coated with hydrophilic polymers having different molecular weights in rats.
Takeuchi, H; Kojima, H; Yamamoto, H; Kawashima, Y
The purpose of this study was to evaluate the circulating properties of liposomes coated with modified polyvinyl alcohol (PVA-R) having different molecular weights (6000, 9000 and 20000). The size controlled liposomes (egg phosphatidylcholine (or distearoylphosphatidylcholine):cholesterol=7:3 in a molar ratio) were prepared by the hydration method followed by sonication. Polymer coated liposomes were prepared by just mixing the resultant liposomal suspension and a polymer solution. The effects of polymer coating were evaluated by measuring the circulation time of the injected liposomes after i.v. administration in rats and the dispersing property of the liposomes in a biological condition. The circulation of the PVA-R coated liposomes was prolonged with increasing the molecular weight of PVA-R. The aggregation and/or fusion of the liposomes in the presence of serum in vitro was also depressed more by coating the liposomes with PVA-R having higher molecular weight. There was a good correlation between the circulation time and the physical stability of non-coated and the various PVA-R coated liposomes. The prolonged circulation time of PVA-R (molecular weight: 20000) coated liposomes (ca. 1.3 mol% coating) was comparable to that of a stealth liposome prepared with 8 mol% of DSPE-PEG (molecular weight of PEG: 2000). PMID:11451499
Topical liposome drugs to come: what the patent literature tells us. A review.
Korting, H C; Blecher, P; Schäfer-Korting, M; Wendel, A
Drug-containing liposomes for topical use in dermatology have been devised during the last 10 years. Most recently the clinical superiority to a conventional gel of a topical glucocorticosteroid liposome preparation for eczema has been demonstrated. To get more insight from what may be expected from future liposome preparations for topical treatment, the pertinent patent literature has been reviewed. PMID:1810984
Fluorescence Behaviour of an Aluminium Octacarboxy Phthalocyanine--NaYGdF4:Yb/Er Nanoparticle Conjugate.
Taylor, Jessica; Litwinski, Christian; Nyokong, Tebello; Antunes, Edith
Using a methanol assisted thermal decomposition approach, sphere shaped NaYGdF4:Yb/Er upconversion nanoparticles (UCNPs) were successfully synthesized. The chemical, spectroscopic and fluorescence properties of the UCNPs were fully characterized. Characteristic upconversion fluorescence emissions were produced by the NPs in the green, red and NIR regions and the NPs were also shown to possess paramagnetic properties. The influence of the UCNPs on the spectroscopic and fluorescence properties of an aluminium octacarboxy phthalocyanine AlOCPc was investigated. Covalent conjugation to an AlOCPc resulted in a large blue shift of the phthalocyanine's Q band, which was accompanied by a decrease in the Pc's fluorescence lifetime in DMSO. By combining the phthalocyanine and upconversion nanoparticle, we present a system capable of multimodal imaging, using both the upconversion nanoparticle's and phthalocyanine's emission, and magnetic resonance imaging (as a result of doping the upconversion nanoparticles with Gd(3+) ions). PMID:25744527
Regioisomer-Free C 4h ?-Tetrakis(tert-butyl)metallo-phthalocyanines: Regioselective Synthesis and Spectral Investigations.
Iida, Norihito; Tanaka, Kenta; Tokunaga, Etsuko; Takahashi, Hiromi; Shibata, Norio
Metal ?-tetrakis(tert-butyl)phthalocyanines are the most commonly used phthalocyanines due to their high solubility, stability, and accessibility. They are commonly used as a mixture of four regioisomers, which arise due to the tert-butyl substituent on the ?-position, and to the best of our knowledge, their regioselective synthesis has yet to be reported. Herein, the C 4h -selective synthesis of ?-tetrakis(tert-butyl)metallophthalocyanines is disclosed. Using tetramerization of ?-trialkylsilyl phthalonitriles with metal salts following acid-mediated desilylation, the desired metallophthalocyanines were obtained in good yields. Upon investigation of regioisomer-free zinc ?-tetrakis(tert-butyl)phthalocyanine using spectroscopy, the C 4h single isomer described here was found to be distinct in the solid state to zinc ?-tetrakis(tert-butyl)phthalocyanine obtained by a conventional method. PMID:25969805
Electron-donating behavior of few-layer graphene in covalent ensembles with electron-accepting phthalocyanines.
Ragoussi, Maria-Eleni; Katsukis, Georgios; Roth, Alexandra; Malig, Jenny; de la Torre, Gema; Guldi, Dirk M; Torres, Tomás
We describe herein the first example of highly exfoliated graphene covalently linked to electron accepting phthalocyanines. The functionalization of the nanocarbon surface with alkylsulfonyl phthalocyanines was attained by means of a "click" chemistry protocol. The new ensemble was fully characterized (thermogravimetric analysis, atomic force microscopy, transmission electron microscopy and Raman, as well as ground-state absorption) and was studied in terms of electron donor-acceptor interactions in the ground and in the excited state. In particular, a series of steady-state and time-resolved spectroscopy experiments demonstrated photoinduced electron transfer from the graphene to the electron-accepting phthalocyanines. This is the first example of an electron donor-acceptor nanoconjugate, that is, few-layer graphene/phthalocyanine, pinpointing the uncommon electron donating character of graphene. PMID:24568604
Time-of-flight study of photoinduced dynamics of copper and manganese phthalocyanine thin films on Si(111)
NASA Astrophysics Data System (ADS)
Ramonova, A. G.; Butkhuzi, T. G.; Abaeva, V. V.; Tvauri, I. V.; Khubezhov, S. A.; Turiev, A. M.; Tsidaeva, N. I.; Magkoev, T. T.
Photoinduced fragmentation and desorption of species from copper phthalocyanine (CuPc) and manganese phthalocyanine 80 nm thick films deposited on Si(111) have been studied by means of atomic force microscopy and time-of-flight mass spectroscopy in an ultra-high vacuum chamber. The main fragments formed under the effect of low-fluence (1-3 mJ cm-2) nanosecond laser light with photon energies of 2.34 and 1.17 eV are the entire phthalocyanine molecule, molecular fragments, atomic Cu and Mn and a Si-substituted CuPc. The latter is presumably due to migration of the Si atom of the underlying support to the vacancy formed after photoejection of the metallic atom out of the phthalocyanine molecule. The mechanism of photofragmentation and desorption is essentially non-thermal involving the metal atom as a key factor.
Pharmacokinetics of poly(hydroxyethyl-l-asparagine)-coated liposomes is superior over that of PEG-coated liposomes at low lipid dose and upon repeated administration.
Romberg, Birgit; Oussoren, Christien; Snel, Cor J; Carstens, Myrra G; Hennink, Wim E; Storm, Gert
'Stealth' liposomes with a poly(ethylene glycol) (PEG) coating are frequently studied for drug delivery and diagnostic purposes because of their prolonged blood circulation kinetics. However, several recent reports have demonstrated that PEG-liposomes are rapidly cleared at single low lipid doses (<1 micromol/kg) and upon repeated administration (time interval between the injections 5 days-4 weeks). Recently, poly(amino acid)-based stealth liposome coatings have been developed as alternative to the PEG-coating. In this study, the pharmacokinetic behavior of liposomes coated with the poly(amino acid) poly(hydroxyethyl-l-asparagine) (PHEA) was evaluated at low lipid doses and upon repeated administration in rats. Blood circulation times and hepatosplenic localization of PHEA-liposomes were assessed after intravenous injection. When administered at a dose of 0.25 micromol/kg or less, PHEA-liposomes showed significantly longer blood circulation times than PEG-liposomes. A second dose of PHEA-liposomes 1 week after the first injection was less rapidly cleared from the circulation than a second dose of PEG-liposomes. Although the mechanisms behind these observations are still not clear yet, the use of PHEA-liposomes appears beneficial when single low lipid doses and/or repeated dosing schedules are being applied. PMID:17223070
Improved syntheses of high hole mobility phthalocyanines: A case of steric assistance in the cyclo-oligomerisation of phthalonitriles.
Tate, Daniel J; Anémian, Rémi; Bushby, Richard J; Nanan, Suwat; Warriner, Stuart L; Whitaker, And Benjamin J
It has been shown that the base-initiated cyclo-oligomerisation of phthalonitriles is favoured by bulky ?-substituents making it possible to obtain the metal-free phthalocyanine directly and in high yield. The phthalocyanine with eight ?-isoheptyl substituents gives a high time-of-flight hole mobility of 0.14 cm(2)·V(-1)·s(-1) within the temperature range of the columnar hexagonal phase, that is 169-189 °C. PMID:22423280
Improved syntheses of high hole mobility phthalocyanines: A case of steric assistance in the cyclo-oligomerisation of phthalonitriles
Tate, Daniel J; Anémian, Rémi; Nanan, Suwat; Warriner, Stuart L; Whitaker, and Benjamin J
Summary It has been shown that the base-initiated cyclo-oligomerisation of phthalonitriles is favoured by bulky ?-substituents making it possible to obtain the metal-free phthalocyanine directly and in high yield. The phthalocyanine with eight ?-isoheptyl substituents gives a high time-of-flight hole mobility of 0.14 cm2·V?1·s?1 within the temperature range of the columnar hexagonal phase, that is 169–189 °C. PMID:22423280
Studies on precellular evolution: the encapsulation of polyribonucleotides by liposomes.
Baeza, I; Ibańez, M; Santiago, J C; Wong, C; Lazcano, A; Oró, J
Liposomes are 5 to 50 micron vesicles with an internal aqueous environment, whose amphiphilic lipidic components self-assemble into systems with at least one double-layered membrane. Liposomes have been suggested as possible models of precellular systems formed in the early Archean Earth from lipids of non-enzymatic origin. Since it is generally accepted that RNA molecules preceded double-stranded DNA molecules as genetic material, we have studied the encapsulation of polyribonucleotides within liposomes made from dipalmitoyl phosphatidylcholine, and from egg yolk phosphatidylcholine to which cholesterol was added in some cases. The liposomes were prepared under anoxic conditions following the reverse phase evaporation method described by Szoka and Papahadjopoulos. Quantitative determinations show that approximately 50% of the available lipids form liposomes, and that up to 5% of the polyribonucleotides can be entrapped by them. We have also studied the encapsulation of polyribonucleotides in the presence of 1) urea and cyanamide, two non-electrolytes that have been used as prebiotic condensing agents, and 2) of Zn++ and Pb++, two cations employed in the non-enzymatic template-directed synthesis of polyribonucleotides from activated nucleotides. PMID:11537243
Topical application of liposomal cobalamin hydrogel for atopic dermatitis therapy.
Jung, Suk Hyun; Cho, Young Sik; Jun, Sung Soo; Koo, Ja Seong; Cheon, Hyae Gyeong; Shin, Byung Cheol
Topical vitamin B12 was shown to be effective for atopic dermatitis. However, vitamin B12 itself is light sensitive and has low skin permeability, thus reducing its therapeutic effectiveness. In the present study, we prepared a liposomal hydrogel of adenosylcobalamin (AdCbl), a vitamin B12 derivative, and investigated possible beneficial effects of AdCbl on atopic dermatitis using an NC/Nga murine atopic dermatitis model. AdCbl was loaded into liposomes prepared by a thin film hydration method using a pH gradient method that employed citric acid buffer solution. This resulted in AdCbl-loaded liposomes that were 106.4 +/- 2.2 nm in size. The loading efficiency was 40% (of the initial AdCbl amount). Lipo-AdCbl had enhanced skin permeability, being about 17-fold compared with AdCbl-gel. Topical administration of Lipo-AdCbl-gel to 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like skin lesions in NC/Nga mice ameliorated lesion intensity scores, dorsal skin thickness, and total serum IgE in a concentration-dependent manner. Other preparations, including AdCbl solution, AdCbl cream, liposomes alone, and a mixture of AdCbl solution and liposomes had little effect. Taken together, our findings indicate that Lipo-AdCbl-gel has protective effects against atopic dermatitis symptoms, and suggest that it may be of benefit in the treatment of human inflammatory skin diseases. PMID:21699082
Dextran sulfate-dependent fusion of liposomes containing cationic stearylamine.
Zschörnig, O; Arnold, K; Richter, W; Ohki, S
The incorporation of the positively charged stearylamine into phosphatidylcholine liposomes was studied by measuring electrophoretic mobilities. Up to a molar ratio SA/PC = 0.5 an increase of the positive zeta potential can be observed. Addition of the negatively charged macromolecule dextran sulfate leads to a change of the sign of the surface potential of the PC/SA liposomes indicating binding of the macromolecule to the surface. This process is accompanied by an increase in turbidity, which is dependent on the molecular weight of the dextran sulfate and the SA concentration (measured by turbidimetry). Using the NBD/Rh and Pyr-PC fluorescence assays the fusion of SA containing liposomes was investigated. A strong influence of the SA content and molecular weight of dextran sulfate on the fusion extent was observed. The fusion extent is proportional to the SA content in the PC membrane and the molecular weight of dextran sulfate. PC/SA/PE liposomes exhibit a higher fusion extent after addition of dextran sulfate compared to PC/SA liposomes indicating that PE additionally destabilizes the bilayer. Freeze-fracture electron microscopy reveals that the reaction products are large complexes composed of multilamellar stacks of tightly packed, straight membranes and aggregated vesicles. The tight packing of the membranes in the stacks (and the narrow contact of the aggregated vesicles) indicates a strong adherence of opposite membrane surfaces induced by dextran sulfate. PMID:1486657
Liposome-templated supramolecular assembly of responsive alginate nanogels.
Hong, Jennifer S; Vreeland, Wyatt N; Lacerda, Silvia H DePaoli; Locascio, Laurie E; Gaitan, Michael; Raghavan, Srinivasa R
Nanosized gel particles (nanogels) are of interest for a variety of applications, including drug delivery and single-molecule encapsulation. Here, we employ the cores of nanoscale liposomes as reaction vessels to template the assembly of calcium alginate nanogels. For our experiments, a liposome formulation with a high bilayer melting temperature (Tm) is selected, and sodium alginate is encapsulated in the liposomal core. The liposomes are then placed in an aqueous buffer containing calcium chloride, and the temperature is raised up to Tm. This allows permeation of Ca2+ ions through the bilayer and into the core, whereupon these ions gel the encapsulated alginate. Subsequently, the lipid bilayer covering the gelled core is removed by the addition of a detergent. The resulting alginate nanogels have a size distribution consistent with that of the template liposomes (ca. 120-200 nm), as confirmed by transmission electron microscopy and light scattering. Nanogels of different average sizes can be synthesized by varying the template dimensions, and the gel size can be further tuned after synthesis by the addition of monovalent salt to the solution. PMID:18338908
Chitosan coated liposomes as an innovative nanocarrier for drugs.
Gonçalves, Manuela C F; Mertins, Omar; Pohlmann, Adriana R; Silveira, Nádya P; Guterres, Sílvia S
Chitosomes are chitosan coated liposomes that represent an alternative to conventional liposomes since they present better stability and bioadhesivity. The aim of this work was to develop and evaluate the physico-chemical stability of melatonin (MEL)-loaded chitosomes as well as to compare their properties with that of MEL loaded liposomes. Structural characteristics of nanovesicles were also studied by dynamic light scattering and small angle X-ray scattering. The liposome and chitosome suspensions presented mean diameters between 150 nm and 254 nm, polydispersity indexes around 0.4, zeta potential values between -38 mV and -28 mV, pH values close to 4.0, MEL content close to 100% and encapsulation efficiency between 34.4% and 60.8%. Small angle X-rays scattering showed the presence of unilamelar structures, which were also observed by transmission electronic microscopy. Stability studies focusing on the particle diameter indicated that, within 90 days, the liposome suspensions had a decrease in mean diameter values and in polydispersity indexes, but no alterations were detected in zeta potentials and MEL content. The chitosome suspensions remained stable in relation to these parameters during 90 days. Multiple light scattering analysis (Turbiscan LAb) corroborated the the findings in the stability studies. The result sets pointed out the physico-chemical stability of chitosomes and the chitosan influence in their supramolecular structure. PMID:22515075
Crosslinked Multilamellar Liposomes for Controlled Delivery of Anticancer Drugs
Joo, Kye-Il; Xiao, Liang; Liu, Shuanglong; Liu, Yarong; Lee, Chi-Lin; Conti, Peter S.; Wong, Michael K.; Li, Zibo; Wang, Pin
Liposomes constitute one of the most popular nanocarriers for the delivery of cancer therapeutics. However, since their potency is limited by incomplete drug release and inherent instability in the presence of serum components, their poor delivery occurs in certain circumstances. In this study, we address these shortcomings and demonstrate an alternative liposomal formulation, termed crosslinked multilamellar liposome (CML). With its properties of improved sustainable drug release kinetics and enhanced vesicle stability, CML can achieve controlled delivery of cancer therapeutics. CML stably encapsulated the anticancer drug doxorubicin (Dox) in the vesicle and exhibited a remarkably controlled rate of release compared to that of the unilamellar liposome (UL) with the same lipid composition or Doxil-like liposome (DLL). Our imaging study demonstrated that the CMLs were mainly internalized through a caveolin-dependent pathway and were further trafficked through the endosome-lysosome compartments. Furthermore, in vivo experiments showed that the CML-Dox formulation reduced systemic toxicity and significantly improved therapeutic activity in inhibiting tumor growth compared to that of UL-Dox or DLL-Dox. This drug packaging technology may therefore provide a new treatment option to better manage cancer and other diseases. PMID:23375392
Liposomes self-assembled from electrosprayed composite microparticles
NASA Astrophysics Data System (ADS)
Yu, Deng-Guang; Yang, Jun-He; Wang, Xia; Tian, Feng
Composite microparticles, consisting of polyvinylpyrrolidone (PVP), naproxen (NAP) and lecithin (PC), have been successfully prepared using an electrospraying process and exploited as templates to manipulate molecular self-assembly for the synthesis of liposomes in situ. Field emission scanning electron microscope (FESEM) and transmission electron microscope (TEM) observations demonstrate that the microparticles have an average diameter of 960 ± 140 nm and a homogeneous structure. X-ray diffraction (XRD) patterns, differential scanning calorimetry (DSC) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) results verify that the building blocks NAP and PC are scattered in the polymer matrix in a molecular way owing to the very fast drying of the electrospraying process and the favorable secondary interactions among the components. FESEM, scanning probe microscope (SPM) and TEM observations demonstrate that the liposomes can be achieved through molecular self-assembly in situ when the microparticles contact water thanks to 'like prefers like' and by means of the confinement effect of the microparticles. The liposomes have an encapsulation rate of 91.3%, and 80.7% of the drug in the liposomes can be freed into the dissolution medium in a sustained way and by a diffusion mechanism over a period of 24 h. The developed strategy not only provides a new, facile, and effective method to assemble and organize molecules of multiple components into liposomes with electrosprayed microparticles as templates, but also opens a new avenue for nanofabrication in a step-by-step and controllable way.
Synthesis and evaluation of glyco-coated liposomes as drug carriers for active targeting in drug delivery systems.
Ueki, Akiharu; Un, Keita; Mino, Yuka; Yoshida, Mitsuru; Kawakami, Shigeru; Ando, Hiromune; Ishida, Hideharu; Yamashita, Fumiyoshi; Hashida, Mitsuru; Kiso, Makoto
Novel sugar-conjugated cholesterols, ?-Gal-, ?-Man-, ?-Man-, ?-Fuc-, and ?-Man-6P-S-?-Ala-Chol, were synthesized and incorporated into liposomes. In vitro experiments using the glyco-coated liposomes showed that the glyco-coated liposomes are efficiently taken up by cells expressing carbohydrate-binding receptors selectively. Glyco-coated liposomes are promising candidates for drug delivery vehicles. PMID:25500195
Evaluation of polyethylene glycol coated liposomes labeled with Tc-99m as a blood pool agent
Phillips, W.T.; Klipper, R.; Goins, B. [Univ. of Texas Health Science Center, San Antonio, TX (United States)
This investigation evaluated Tc-99m liposomes coated with polyethylene glycol (PEG) as a blood pool agent in comparison with Tc-99m liposomes carrying no surface charge (Neutral) and with Tc-99m autologous red cells. Liposomes (135 nm diameter) encapsulating glutathione were labeled with Tc-99m using the lipophilic chelator, HMPAO as previously described. Autologous red cells were labeled using an Ultratag kit. Labeling efficiencies averaged 66%, 52%, and 97% for the PEG liposomes. Neutral liposomes, and red cells, respectively. Rabbits (3-3.5 Kg) were injected IV via ear vein with 2.0 mls of PEG liposomes (2 mCi, 17 mg phospholipid/Kg body weight, n=5). Neutral liposomes (1.3 mCi, 17 mg phospholipid/Kg body weight, n=4), or red cells (2.6 mCi, n=2). Gamma camera images were acquired at 5,22, and 45 minutes, and 2,20,and 44 hours post-injection. Blood samples were obtained at each time point to determine clearance kinetics. Circulation half lives of both Tc-99m liposome formulations were longer than Tc-99m red cells (8 hrs), with the half life of PEG liposomes (35 hrs) 1.6 times longer than Neutral liposomes (22 hrs). In vivo stability of the Tc-99m label was excellent for the liposomes with only 3.5-4% bladder activity at 45 minutes compared to 12% bladder activity for the red cells. Excellent blood pool images were obtained for the PEG liposomes in the rabbit. Heart/liver ratios calculated from region of interest analysis of 45 minutes images were 1.9, 1.5, and 1.7 for PEG liposomes, Neutral liposomes and red cells. This study demonstrates the feasibility of using Tc-99m PEG liposomes to perform gated cardiac blood pool and rapid gastrointestinal bleeding studies.
Anti-tumor activity of liposome encapsulated fluoroorotic acid as a single agent and in combination with liposome irinotecan.
Riviere, Kareen; Kieler-Ferguson, Heidi M; Jerger, Katherine; Szoka, Francis C
To test the hypothesis that co-delivery of synergistic drug combinations in the same liposome provides a better anti-tumor effect than the drugs administered in separate liposomes, fluoroorotic acid (FOA) alone and in combination with irinotecan (IRN) were encapsulated in liposomes and evaluated for their anti-tumor activity in the C26 colon carcinoma mouse model. A new chaotropic loading strategy was devised wherein FOA was dissolved in 7 M urea to increase its solubility. This enabled the passive loading of FOA into liposomes at a high concentration. IRN was remote loaded into liposomes that contained the ammonium salt of the multi-valent 1,2,3,4-butanetetracarboxylic acid with a greater than 90% efficiency and at a drug to lipid ratio of 0.2:1. When the two molecules were loaded into the same liposome, FOA was used to remote load IRN. Modulation of the drug/lipid ratio, temperature, and loading time allowed for consistent co-encapsulation of FOA+IRN at various molar ratios. The anti-tumor activity of L-FOA, L-IRN, L-FOA-IRN (5:1), and the L-FOA+L-IRN mixture (5:1) were examined in the C26 mouse model. The maximum tolerated dose of L-FOA was 10 mg/kg given weekly as compared to 100 mg/kg of the non-encapsulated FOA. Delivering two drugs in the same liposome provided a statistically better anti-tumor effect than delivering the drugs in separate liposomes at the same drug ratio. However, the synergistic activity of the 5:1 ratio of free drugs measured on C26 cells in vitro was not observed in the C26 tumor mouse model. These findings point out the challenges to the design of synergistic treatment protocols based upon results from in vitro cytotoxicity studies. L-FOA at 10 mg/kg as a single agent provided the best anti-tumor efficacy which supports previous suggestions that L-FOA has useful properties as a liposome dependent drug. PMID:21600250
Multivesicular liposomal bupivacaine at the sciatic nerve
McAlvin, J. Brian; Padera, Robert F.; Shankarappa, Sahadev A.; Reznor, Gally; Kwon, Albert H.; Chiang, Homer; Yang, Jason; Kohane, Daniel S.
Clinical translation of sustained release formulations for local anesthetics has been limited by adverse tissue reaction. Exparel™ (DepoFoam bupivacaine) is a new liposomal local anesthetic formulation whose biocompatibility near nerve tissue is not well characterized. Exparel™ injection caused sciatic nerve blockade in rats lasting 240 minutes compared to 120 minutes for 0.5% (w/v) bupivacaine HCl and 210 minutes for 1.31% (w/v) bupivacaine HCl (same bupivacaine content as Exparel™). On histologic sections four days after injection, median inflammation scores in the Exparel™ group (2.5 of 4) were slightly higher than in groups treated with bupivacaine solutions (score 2). Myotoxicity scores in the Exparel™ group (2.5 of 6) were similar to in the 0.5% (w/v) bupivacaine HCl group (3), but significantly less than in the 1.31% (w/v) bupivacaine HCl group (5). After two weeks, inflammation from Exparel™ (score 2 of 6) was greater than from 0.5% (w/v) bupivacaine HCl (1) and similar to that from 1.31% (w/v) bupivacaine HCl (1). Myotoxicity in all three groups was not statistically significantly different. No neurotoxicity was detected in any group. Tissue reaction to Exparel™ was similar to that of 0.5% (w/v) bupivacaine HCl. Surveillance for local tissue injury will be important during future clinical evaluation. PMID:24612918
Clearance of liposomal gadolinium: in vivo decomplexation.
Unger, E C; Fritz, T A; Tilcock, C; New, T E
The contrast agents gadolinium-DTPA (diethylenetriaminepentaacetic acid), Gd-DOTA (tetraazacyclododecanetetraacetic acid), and Gd-HP-DO3A (1,4,7-tris[carboxymethyl]-10-[2' hydroxypropyl]-1,4,7,10-tetraazacyclododecane) are used in humans as extracellular contrast agents. Although free Gd+ ion is toxic, the intact Gd3+ complexes are rapidly excreted and are relatively nontoxic. Decomplexation with release of free gadolinium is a relevant clinical concern in patients with altered renal clearance. Blood pool contrast agents currently under development may have longer clearance half-lives and be more prone to decomplexation. The present study was designed to evaluate the clearance of liposomally encapsulated Gd3+ complexes (DTPA, DOTA, and HP-DO3A). The macrocyclic compounds had more rapid and complete clearance than DTPA (P less than .05). Parallel studies with carbon-14 and Gd-153-labeled complexes showed significant differences (P less than .05) in the amount of these isotopes retained in the heart, kidney, lungs, and spleen, providing strong supportive evidence for in vivo decomplexation. PMID:1823174
The organ distribution of liposome-encapsulated and free cobalt in rats. Liposomes decrease the cardiac uptake of the metal
Garcia, R.; Eskelson, C.D.; Chvapil, M. (Univ. of Arizona, Tucson (USA)); Szebeni, J. (Univ. of Arizona, Tucson (USA) National Institute of Food Hygiene and Nutrition, Budapest (Hungary))
Rats were administered intravenously liposome-encapsulated or free cobalt, and the organ distribution of the metal was explored using Co{sup 57} tracer. Two hours after administration, the cobalt level in the heart was about 40 % of the control when given in sphingomyelin (SM)/cholesterol (CH) (1:1 mole ratio) liposomes. These vesicles also tended to decrease the uptake of cobalt in the kidney and the carcass, and to increase it in the spleen and the bones. Liposomes prepared from soybean phosphatidylcholine (SPC)/CH (1:1) had no effect on the uptake of cobalt in the heart, whereas increased its level in the spleen, liver and lung. The time-course of cobalt deposition in the organs displayed substantial variation with the different preparations. Most importantly, no buildup of cobalt level was observed in the heart when the metal was administered in SM/CH vesicles. While confirming known effects of liposomes on the organ-distribution of entrapped drugs, our findings suggest that administration of cobalt in SM/CH liposome-encapsulated form may result in decreased cardiotoxicity and thus increased safety of cobalt-treatment in some anemias.
Enhanced bactericidal potency of nanoliposomes by modification of the fusion activity between liposomes and bacterium
Ma, Yufan; Wang, Zhao; Zhao, Wen; Lu, Tingli; Wang, Rutao; Mei, Qibing; Chen, Tao
Background Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of Pseudomonas to conventional antibiotics made it imperative to develop new liposome formulations to overcome these mechanisms, and investigate the fusion between liposome and bacterium. Methods The rigidity, stability and charge properties of phospholipid vesicles were modified by varying the cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), and negatively charged lipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol sodium salt (DMPG), 1,2-dimyristoyl-sn-glycero-3-phopho-L-serine sodium salt (DMPS), 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA), nature phosphatidylserine sodium salt from brain and nature phosphatidylinositol sodium salt from soybean concentrations in liposomes. Liposomal fusion with intact bacteria was monitored using a lipid-mixing assay. Results It was discovered that the fluid liposomes-bacterium fusion is not dependent on liposomal size and lamellarity. A similar degree of fusion was observed for liposomes with a particle size from 100 to 800 nm. The fluidity of liposomes is an essential pre-request for liposomes fusion with bacteria. Fusion was almost completely inhibited by incorporation of cholesterol into fluid liposomes. The increase in the amount of negative charges in fluid liposomes reduces fluid liposomes-bacteria fusion when tested without calcium cations due to electric repulsion, but addition of calcium cations brings the fusion level of fluid liposomes to similar or higher levels. Among the negative phospholipids examined, DMPA gave the highest degree of fusion, DMPS and DMPG had intermediate fusion levels, and PI resulted in the lowest degree of fusion. Furthermore, the fluid liposomal encapsulated tobramycin was prepared, and the bactericidal effect occurred more quickly when bacteria were cultured with liposomal encapsulated tobramycin. Conclusion The bactericidal potency of fluid liposomes is dramatically enhanced with respect to fusion ability when the fusogenic lipid, DOPE, is included. Regardless of changes in liposome composition, fluid liposomes-bacterium fusion is universally enhanced by calcium ions. The information obtained in this study will increase our understanding of fluid liposomal action mechanisms, and help in optimizing the new generation of fluid liposomal formulations for the treatment of pulmonary bacterial infections. PMID:23847417
Mutants of listeriolysin O for enhanced liposomal delivery of macromolecules.
Walls, Zachary F; Goodell, Stefanie; Andrews, Chasity D; Mathis, Jonathan; Lee, Kyung-Dall
Delivery of macromolecules into the cytosolic space of eukaryotic cells is a pressing challenge in biopharmaceutics. Macromolecules are often encapsulated into liposomes for protection and improved distribution, but the their size often induces endocytosis of the vehicle at the target site, leading to degradation of the cargo. Listeriolysin O is a key virulence factor of Listeria monocytogenes that forms pores in the endosomal membrane, ultimately allowing the bacterium to escape into the cytosol. This function of LLO has been used to improve cytosolic delivery of liposomally encapsulated macromolecules in a number of instances, but its innate toxicity and immunogenicity have prevented it from achieving widespread acceptance. Through site-directed mutagenesis, this study establishes a mutant of LLO (C484S) with enhanced activity, allowing for a reduction in the amount of LLO used for future applications in liposomal drug delivery. PMID:23416330
Recruitment of coat proteins to liposomes and peptidoliposomes.
Huser, Sonja; Suri, Gregor; Crottet, Pascal; Spiess, Martin
Intracellular transport within the cell is generally mediated by membrane vesicles. Their formation is typically initiated by activation of small GTPases that then recruit cytosolic proteins to the membrane surface to form a coat, interact with cargo and accessory proteins, and deform the lipid bilayer to produce a transport vesicle. Liposomes proved to be a useful tool to study the molecular mechanisms of these processes in vitro. Here we describe the use of liposomes and peptidoliposomes presenting lipid-coupled cytosolic tails of cargo proteins for the in vitro analysis of the membrane recruitment of AP-1 adaptors in the process of forming AP-1/clathrin coats. AP-1 recruitment is mediated by the GTPase Arf1 and requires specific lipids and cargo signals. Interaction with cargo induces AP-1 oligomerization already in the absence of clathrin. Without cargo peptides, accessory proteins, such as amphiphysin 2, can be identified that stabilize AP-1 binding to liposomal membranes. PMID:25702111
Ultraviolet- and sunlight-induced lipid peroxidation in liposomal membrane
Mandal, T.K.; Chatterjee, S.N.
Ultraviolet radiation and sunlight caused lipid peroxidation in the liposomal membrane (as detected by measurement of the oxidation index, A/sub 233//A/sub 215/, and the amount of malondialdehyde formed) and made the membrane leaky (as revealed by the release of the trapped chromate anions). The oxidation index and the formation of malondialdehyde increased linearly with increasing dose of radiation and depended significantly on the dose rate. The effects were smaller in liposomes derived from Vibrio cholerae phospholipid than in those derived from egg lecithin. The effects of the radiation dose and dose rate on hemolysis and peroxidation (MDA formation) of the erythrocyte membrane followed a similar pattern. A direct correlation between the percentage leakage of chromate (Y) and the oxidation index (X) of the liposomal system was obtained as Y = 236.5 x X.
Liposomal extended-release bupivacaine for postsurgical analgesia
Lambrechts, Mark; O'Brien, Michael J; Savoie, Felix H; You, Zongbing
When physicians consider which analgesia to use postsurgery, the primary goal is to relieve pain with minimal adverse side effects. Bupivacaine, a commonly used analgesic, has been formulated into an aqueous suspension of multivesicular liposomes that provide long-lasting analgesia for up to 72 hours, while avoiding the adverse side effects of opioids. The increased efficacy of liposomal extended-release bupivacaine, compared to bupivacaine hydrochloride, has promoted its usage in a variety of surgeries including hemorrhoidectomy, bunionectomy, inguinal hernia repair, total knee arthroplasty, and augmentation mammoplasty. However, like other bupivacaine formulations, the liposomal extended-release bupivacaine does have some side effects. In this brief review, we provide an update of the current knowledge in the use of bupivacaine for postsurgical analgesia. PMID:24043932
Improved Photodynamic Efficacy of Zn(II) Phthalocyanines via Glycerol Substitution
Chin, Yunni; Lim, Siang Hui; Zorlu, Yunus; Ahsen, Vefa; Kiew, Lik Voon; Chung, Lip Yong; Dumoulin, Fabienne; Lee, Hong Boon
Phthalocyanines are excellent photosensitizers for photodynamic therapy as they have strong absorbance in the near infra-red region which is most relevant for in vivo activation in deeper tissular regions. However, most phthalocyanines present two major challenges, ie, a strong tendency to aggregate and low water-solubility, limiting their effective usage clinically. In the present study, we evaluated the potential enhancement capability of glycerol substitution on the photodynamic properties of zinc (II) phthalocyanines (ZnPc). Three glycerol substituted ZnPc, 1–3, (tetra peripherally, tetra non-peripherally and mono iodinated tri non-peripherally respectively) were evaluated in terms of their spectroscopic properties, rate of singlet oxygen generation, partition coefficient (log P), intracellular uptake, photo-induced cytotoxicity and vascular occlusion efficiency. Tetrasulfonated ZnPc (ZnPcS4) was included as a reference compound. Here, we showed that 1–3 exhibited 10–100 nm red-shifted absorption peaks with higher molar absorptivity, and at least two-fold greater singlet oxygen generation rates compared to ZnPcS4. Meanwhile, phthalocyanines 1 and 2 showed more hydrophilic log P values than 3 consistent with the number of glycerol attachments but 3 was most readily taken up by cells compared to the rest. Both phthalocyanines 2 and 3 exhibited potent phototoxicity against MCF-7, HCT-116 and HSC-2 cancer cell-lines with IC50 ranging 2.8–3.2 µM and 0.04–0.06 µM respectively, while 1 and ZnPcS4 (up to 100 µM) failed to yield determinable IC50 values. In terms of vascular occlusion efficiency, phthalocyanine 3 showed better effects than 2 by causing total occlusion of vessels with diameter <70 µm of the chorioallantoic membrane. Meanwhile, no detectable vascular occlusion was observed for ZnPcS4 with treatment under similar experimental conditions. These findings provide evidence that glycerol substitution, in particular in structures 2 and 3, is able to improve the photodynamic properties of ZnPc. PMID:24840576
99mTc-labeled Therapeutic Inhaled Amikacin Loaded Liposomes
Lee, Jae-Ho; Cheng, Kenneth T.; Malinin, Vladimir; Li, Zhili; Yao, Zhengsheng; Lee, Sung-Jin; Gould, Christine M.; Olivier, Kenneth N.; Chen, Clara; Perkins, Walter R.; Paik, Chang H.
The radiolabeling of the liposome surface can be a useful tool for in vivo tracking of therapeutic drug loaded liposomes. We investigated radiolabeling therapeutic drug (i.e., an antibiotic, amikacin) loaded liposomes with 99mTc, nebulization properties of 99mTc-labeled liposomal amikacin for inhalation (99mTc-LAI), and its stability by size exclusion low pressure liquid chromatography (LPLC). LAI was reacted with 99mTc using SnCl2 dissolved in ascorbic acid as a reducing agent for 10 min at room temperature. The labeled products were then purified by anion exchange resin. The purified 99mTc-LAI in 1.5% NaCl solution was incubated at 4oC to assess its stability by LPLC. The purified 99mTc-LAI was subjected to studies with a clinically used nebulizer (PARI eFlow®) and the Anderson Cascade Impactor (ACI). The use of ascorbic acid at 0.91 mM resulted in a quantitative labeling efficiency. The LPLC profile showed that the liposomal peak of LAI detected by a UV monitor at both 200 nm and 254 nm overlapped with the radioactivity peak of 99mTc-LAI, indicating that 99mTc-LAI is suitable for tracing LAI. The ACI study demonstrated that the aerosol droplet size distribution determined gravimetrically was similar to that determined by radioactivity. The liposome surface labeling method using SnCl2 in 0.91mM ascorbic acid produced 99mTc-LAI with a high labeling efficiency and stability that are adequate to evaluate the deposition and clearance of inhaled LAI in the lung by gamma scintigraphy. PMID:23879241
(99m)Tc-labeled therapeutic inhaled amikacin loaded liposomes.
Lee, Jae-Ho; Cheng, Kenneth T; Malinin, Vladimir; Li, Zhili; Yao, Zhengsheng; Lee, Sung-Jin; Gould, Christine M; Olivier, Kenneth N; Chen, Clara; Perkins, Walter R; Paik, Chang H
The radiolabeling of the liposome surface can be a useful tool for in vivo tracking of therapeutic drug loaded liposomes. We investigated radiolabeling therapeutic drug (i.e. an antibiotic, amikacin) loaded liposomes with (99m)Tc, nebulization properties of (99m)Tc-labeled liposomal amikacin for inhalation ((99m)Tc-LAI), and its stability by size exclusion low-pressure liquid chromatography (LPLC). LAI was reacted with (99m)Tc using SnCl2 dissolved in ascorbic acid as a reducing agent for 10?min at room temperature. The labeled products were then purified by anion exchange resin. The purified (99m)Tc-LAI in 1.5% NaCl solution was incubated at 4?°C to assess its stability by LPLC. The purified (99m)Tc-LAI was subjected to studies with a clinically used nebulizer (PARI eFlow®) and the Anderson Cascade Impactor (ACI). The use of ascorbic acid at 0.91?mM resulted in a quantitative labeling efficiency. The LPLC profile showed that the liposomal peak of LAI detected by a UV monitor at both 200?nm and 254?nm overlapped with the radioactivity peak of (99m)Tc-LAI, indicating that (99m)Tc-LAI is suitable for tracing LAI. The ACI study demonstrated that the aerosol droplet size distribution determined gravimetrically was similar to that determined by radioactivity. The liposome surface labeling method using SnCl? in 0.91?mM ascorbic acid produced (99m)Tc-LAI with a high labeling efficiency and stability that are adequate to evaluate the deposition and clearance of inhaled LAI in the lung by gamma scintigraphy. PMID:23879241
Arrays of lipid bilayers and liposomes on patterned polyelectrolyte templates.
Kohli, Neeraj; Vaidya, Sachin; Ofoli, Robert Y; Worden, Robert M; Lee, Ilsoon
This paper presents novel methods to produce arrays of lipid bilayers and liposomes on patterned polyelectrolyte multilayers. We created the arrays by exposing patterns of poly(dimethyldiallylammonium chloride) (PDAC), polyethylene glycol (m-dPEG) acid, and poly(allylamine hydrochloride) (PAH) on polyelectrolyte multilayers (PEMs) to liposomes of various compositions. The resulting interfaces were characterized by total internal reflection fluorescence microscopy (TIRFM), fluorescence recovery after pattern photobleaching (FRAPP), quartz crystal microbalance (QCM), and fluorescence microscopy. Liposomes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phosphate (monosodium salt) (DOPA) were found to preferentially adsorb on PDAC and PAH surfaces. On the other hand, liposome adsorption on sulfonated poly(styrene) (SPS) surfaces was minimal, due to electrostatic repulsion between the negatively charged liposomes and the SPS-coated surface. Surfaces coated with m-dPEG acid were also found to resist liposome adsorption. We exploited these results to create arrays of lipid bilayers by exposing PDAC, PAH and m-dPEG patterned substrates to DOPA/DOPC vesicles of various compositions. The patterned substrates were created by stamping PDAC (or PAH) on SPS-topped multilayers, and m-dPEG acid on PDAC-topped multilayers, respectively. This technique can be used to produce functional biomimetic interfaces for potential applications in biosensors and biocatalysis, for creating arrays that could be used for high-throughput screening of compounds that interact with cell membranes, and for probing, and possibly controlling, interactions between living cells and synthetic membranes. PMID:16790245
Effect of Dibucaine on Phase Behavior of Ternary Liposome
Kazunari Yoshida; Akito Takashima; Izumi Nishio
We investigated the effect of Dibucaine hydrochloride (DC$\\cdot$HCl), one of the local anesthetics, on phase behavior of ternary liposome composed of dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), and cholesterol (Chol). The large DOPC/DPPC/Chol liposome, that is directly observable by optical microscope, is commonly known to be laterally separated into liquid-ordered (Lo) phase (raft-like domain) and liquid-disordered (Ld) phase under certain conditions and is useful for study of lipid-raft-like domains as a simple model system. In order to confirm the effect of DC$\\cdot$HCl on a miscibility transition temperature, $T_{\\rm c}$, of the ternary liposome, we observed the liposomes with three concentrations, 0, 0.05, and 0.2~mM, of DC$\\cdot$HCl at various temperatures. In addition, we calculated the angle-averaged two-dimensional autocorrelation (2D-AC) functions in order to quantify the phase behavior. The results of these observations and calculations revealed that the DC$\\cdot$HCl molecules induce the reduction of $T_{\\rm c}$ of the ternary liposome. Furthermore, we calculated the circularity of Lo domain in order to confirm the change in the line tension of the Lo/Ld phase boundary and revealed that the insertion of the DC molecules induces the reduction of line tension. In terms of the critical phenomena, we conclude that the insertion of the DC molecules induces the reduction of the $T_{\\rm c}$ of the ternary liposome due to reduction of line tension. This suggests that the DC molecules may disturb function of ion channels via affecting the lipid bilayers which surround ion channels.
PEG Minocycline-Liposomes Ameliorate CNS Autoimmune Disease
Ben, Li-Hong; Cravens, Petra D.; Singh, Mahendra P.; Frohman, Elliot M.; Eagar, Todd N.; Racke, Michael K.; Kieseier, Bernd C.; Stüve, Olaf
Background Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS). Minocycline, a potent inhibitor of matrix metalloproteinase (MMP)-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG) minocycline liposomes are effective in treating EAE. Findings Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs), we determined that PEG minocycline-liposome preparations stabilized with CaCl2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number. Conclusions Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS. PMID:19127301
In vivo antitumor activity of camptothecin incorporated in liposomes formulated with an artificial lipid and human serum albumin
Masato Watanabe; Kumi Kawano; Kazunori Toma; Yoshiyuki Hattori; Yoshie Maitani
Camptothecin (CPT) is a strong antitumor agent, but its use limited by its low solubility and the instability of the active lactone form. To overcome these difficulties, liposomes incorporating CPT (CPT liposomes) were designed and tested. CPT liposomes were formulated by the addition of 3,5-bis(dodecyloxy)benzoic acid (DB) to polyethylene glycol-containing liposomes, and by coating the surface of the liposomes with
Pharmacokinetics of poly(hydroxyethyl- l-asparagine)-coated liposomes is superior over that of PEG-coated liposomes at low lipid dose and upon repeated administration
Birgit Romberg; Christien Oussoren; Cor J. Snel; Myrra G. Carstens; Wim E. Hennink; Gert Storm
'Stealth' liposomes with a poly(ethylene glycol) (PEG) coating are frequently studied for drug delivery and diagnostic purposes because of their prolonged blood circulation kinetics. However, several recent reports have demonstrated that PEG-liposomes are rapidly cleared at single low lipid doses (<1 ?mol\\/kg) and upon repeated administration (time interval between the injections 5 days–4 weeks). Recently, poly(amino acid)-based stealth liposome coatings have
Cationic surface charge enhances early regional deposition of liposomes after intracarotid injection.
Joshi, Shailendra; Singh-Moon, Rajinder; Wang, Mei; Chaudhuri, Durba B; Ellis, Jason A; Bruce, Jeffrey N; Bigio, Irving J; Straubinger, Robert M
Rapid first pass uptake of drugs is necessary to increase tissue deposition after intraarterial (IA) injection. Here we tested whether brain tissue deposition of a nanoparticulate liposomal carrier could be enhanced by coordinated manipulation of liposome surface charge and physiological parameters, such as IA injection during transient cerebral hypoperfusion (TCH). Different degrees of blood-brain barrier disruption were induced by focused ultrasound in three sets of Sprague-Dawley rats. Brain tissue retention was then compared for anionic, cationic, and charge-neutral liposomes after IA injection combined with TCH. The liposomes contained a non-exchangeable carbocyanine membrane optical label that could be quantified using diffuse reflectance spectroscopy (DRS) or visualized by multispectral imaging. Real-time concentration-time curves in brain were obtained after each liposomal injection. Having observed greater tissue retention of cationic liposomes compared to other liposomes in all three groups, we tested uptake of cationic liposomes in C6 tumor bearing rats. DRS and multispectral imaging of postmortem sections revealed increased liposomal uptake by the C6 brain tumor as compared to non-tumor contralateral hemisphere. We conclude that regional deposition of liposomes can be enhanced without BBB disruption using IA injection of cationic liposomal formulations in healthy and C6 tumor bearing rats. PMID:25195130
Self-assembly and cytotoxicity study of PEG-modified ursolic acid liposomes.
Zhao, Tingting; Liu, Yanping; Gao, Zhengrong; Gao, Dawei; Li, Nan; Bian, Yanhong; Dai, Kun; Liu, Zhiwei
While ursolic acid (UA), one of the most broadly known triterpene compounds, has proved to be effective in cancer therapy, the applications of UA is limited due to its poor aqueous solubility and low bioavailability. The aim of our study was to prolong circulation time and enhance uptake of liposomes in tumor tissues through the modification of UA liposomes via water-soluble polyethylene glycol (PEG). In addition, this research also focuses on physicochemical properties of the liposome formulations, including encapsulation efficiency, particle morphology, size, stability, release rate in vitro and cytotoxicity test. The obtained liposomes were spherical particles with mean particle diameters around 100-200nm. And the Fourier transform infrared spectroscopy (FTIR) indicated that PEG had been anchored successfully to the liposomes. Based on our experimental data achieved, PEG-modified UA liposomes possessed higher stability than conventional liposomes, and the release rate of UA from PEG-modified liposomes was slower when compared with those of UA solution and conventional liposomes. Meanwhile, the liposomal UA showed relatively low cytotoxic effect than UA conventional liposomes within 24h, which was consistent with their release rates. PMID:26042707
Chlorophyll-quinone photochemical electron transfer in liposomes
Hurley, J.K.; Castelli, F.; Tollin, G.
A study is described which involves the reduction of electron acceptors (quinones) by photoexcited chlorophyll (Chl). The experimental samples consisted of Chl a (from spinach) incorporated into phosphatidylcholine (either synthetic or from hen egg yolks) liposomes suspended in 10 mM phosphate buffer (pH 7.0). The quinones were either present during liposome formation or added later, depending on their water solubility. The measurement technique employed was laser flash photolysis. Results have provided considerable insight into the ways in which membranes may modify the photochemical properties of Chl by allowing molecular compartmentalization and by permitting cooperative interactions.
Development of a new resistant liposome coated with polysaccharide film for cosmetic application.
Belhaj, Nabila; Arnaud, Jean Pierre; Loing, Estelle; Bézivin, Carine
The aim of our study was to elaborate a resistant liposome that can be used in cosmetic formulations containing high amounts of surfactants and electrolytes. The stability of liposomes was increased via hydrophobized polysaccharide (Stearoyl Inulin) by anchoring its stearic acid tail into liposome bilayer. Coated and noncoated liposomes were prepared under the same conditions and their morphology, size, and resistance to surfactants and electrolytes were evaluated. We established that coated lipbsomes were more resistant to surfactants and electrolytes. It seems that a coating of polysaccharides prevents liposome destabilization in the presence of high amounts of surfactants and electrolytes. Moreover, the ability of coated liposomes to improve the skin delivery of active molecules was evaluated. Coated liposomes increased the efficacy of magnesium chloride by improving its skin availability. PMID:25423742
Liposomal carfilzomib nanoparticles effectively target multiple myeloma cells and demonstrate enhanced efficacy in vivo.
Ashley, Jonathan D; Stefanick, Jared F; Schroeder, Valerie A; Suckow, Mark A; Alves, Nathan J; Suzuki, Rikio; Kikuchi, Shohei; Hideshima, Teru; Anderson, Kenneth C; Kiziltepe, Tanyel; Bilgicer, Basar
Carfilzomib, a recently FDA-approved proteasome inhibitor, has remarkable anti-myeloma (MM) activity. However, its effectiveness is limited by associated severe side-effects, short circulation half-life, and limited solubility. Here, we report the engineering of liposomal carfilzomib nanoparticles to overcome these problems and enhance the therapeutic efficacy of carfilzomib by increasing tumoral drug accumulation while decreasing systemic toxicity. In our design, carfilzomib was loaded into the bilayer of liposomes to yield stable and reproducible liposomal nanoparticles. Liposomal carfilzomib nanoparticles were efficiently taken up by MM cells, demonstrated proteasome inhibition, induced apoptosis, and exhibited enhanced cytotoxicity against MM cells. In vivo, liposomal carfilzomib demonstrated significant tumor growth inhibition and dramatically reduced overall systemic toxicity compared to free carfilzomib. Finally, liposomal carfilzomib demonstrated enhanced synergy in combination with doxorubicin. Taken together, this study establishes the successful synthesis of liposomal carfilzomib nanoparticles that demonstrates improved therapeutic index and the potential to improve patient outcome in MM. PMID:25312543
Poly(amino acid)s: promising enzymatically degradable stealth coatings for liposomes.
Romberg, Birgit; Metselaar, Josbert M; Baranyi, Lajos; Snel, Cor J; Bünger, Rolf; Hennink, Wim E; Szebeni, Janos; Storm, Gert
Poly(amino acid)s (PAAs) were evaluated as coating polymers for long-circulating liposomes. The pharmacokinetics of PAA-coated liposomes were assessed in rats. Prolonged circulation times were obtained, comparable to those reported for poly(ethylene glycol) (PEG)-liposomes. Besides, the enzymatic degradability of PAAs was studied. PAAs - in free as well as liposome-associated form - are degradable by proteases, which is beneficial for reducing the risks of accumulation in vivo. Furthermore, complement activation by PAA-liposomes was evaluated in vitro and in vivo. Like other liposome types, they appear to activate the complement system. However, a role of endotoxin contamination of the PAA-liposome formulations used cannot be excluded in our complement activation studies. PMID:17145145
Development and Evaluation of Chitosan-Coated Liposomes for Oral DNA Vaccine: The Improvement of Peyer's Patch Targeting Using a Polyplex-Loaded Liposomes
Sunee Channarong; Wanpen Chaicumpa; Nuttanan Sinchaipanid; Ampol Mitrevej
The aim of this study was to develop chitosan-coated and polyplex-loaded liposomes (PLLs) containing DNA vaccine for Peyer's\\u000a patch targeting. Plain liposomes carrying plasmid pRc\\/CMV-HBs were prepared by the reverse-phase evaporation method. Chitosan\\u000a coating was carried out by incubation of the liposomal suspensions with chitosan solution. Main lipid components of liposomes\\u000a were phosphatidylcholine\\/cholesterol. Sodium deoxycholate and dicetyl phosphate were used
N-trimethyl chitosan chloride-coated liposomes for the oral delivery of curcumin.
Chen, Huanlei; Wu, Jun; Sun, Min; Guo, Chenyu; Yu, Aihua; Cao, Fengliang; Zhao, Liyan; Tan, Qi; Zhai, Guangxi
The aims of this study were to design the formulation of curcumin (CUR) liposomes coated with N-trimethyl chitosan chloride (TMC) and to evaluate in vitro release characteristics and in vivo pharmacokinetics and bioavailability of TMC-coated CUR liposomes in rats. The structure of synthesized TMC was examined by infrared spectroscopy, with the presence of trimethyl groups, and by proton nuclear magnetic resonance spectroscopy, indicating the high degree of substitution quaternization (65.6%). Liposomes, composed of soybean phosphotidylcholine, cholestrol, and D-?-tocopheryl polyethylene glycol 1000 succinate, were prepared by a thin-film dispersion method. Characteristics of the CUR liposomes, including entrapment efficiency (86.67%), drug-loading efficiency (2.33%), morphology, particle size (221.4?nm for uncoated liposomes and 657.7?nm for TMC-coated liposomes), and zeta potential (-9.63 mV for uncoated liposomes and +15.64 mV for TMC-coated liposomes) were investigated. Uncoated CUR liposomes and TMC-coated CUR liposomes showed a similar in vitro release profile. Nearly 50% of CUR was released from liposomes, whereas 80% of CUR was released from CUR propylene glycol solution. CUR incorporated into TMC-coated liposomes exhibited different pharmacokinetic parameters and enhanced bioavailability (C(max)?=?46.13 ?g/L, t(1/2)?=?12.05 hours, AUC?=?416.58 ?g/L·h), compared with CUR encapsulated by uncoated liposomes (C(max)?=?32.12 ?g/L, t(1/2)?=?9.79 hours, AUC?=?263.77 ?g/L·h) and CUR suspension (C(max)?=?35.46 ?g/L, t(1/2)?=?3.85 hours, AUC?=?244.77 ?g/L·h). In conclusion, oral delivery of coated CUR liposomes is a promising strategy for poorly water-soluble CUR. PMID:22007962
PLGA/liposome hybrid nanoparticles for short-chain ceramide delivery
Zou, Peng; Stern, Stephan T.; Sun, Duxin
Purpose Rapid premature release of lipophilic drugs from liposomal lipid bilayer to plasma proteins and biological membranes is a challenge for targeted drug delivery. The purpose of this study is to reduce premature release of lipophilic short-chain ceramides by encapsulating ceramides into liposomal aqueous interior with the aid of poly( lactic-coglycolicacid) (PLGA). Methods BODIPY FL labeled ceramide (FL-ceramide) and BODIPY-TR labeled ceramide (TR-ceramide) were encapsulated into carboxy-terminated PLGA nanoparticles. The negatively charged PLGA nanoparticles were then encapsulated into cationic liposomes to obtain PLGA/liposome hybrids. As a control, FL-ceramide and/or TR ceramide co-loaded liposomes without PLGA were prepared. The release of ceramides from PLGA/liposome hybrids and liposomes in rat plasma, cultured MDA-MB-231 cells, and rat blood circulation was compared using fluorescence resonance energy transfer (FRET) between FL-ceramide (donor) and TR-ceramide (acceptor). Results FRET analysis showed that FL-ceramide and TR-ceramide in liposomal lipid bilayer were rapidly released during incubation with rat plasma. In contrast, the FL-ceramide and TR-ceramide in PLGA/liposome hybrids showed extended release. FRET images of cells revealed that ceramides in liposomal bilayer were rapidly transferred to cell membranes. In contrast, ceramides in PLGA/liposome hybrids were internalized into cells with nanoparticles simultaneously. Upon intravenous administration to rats, ceramides encapsulated in liposomal bilayer were completely released in 2 minutes. In contrast, ceramides encapsulated in the PLGA core were retained in PLGA/liposome hybrids for 4 hours. Conclusions The PLGA/liposome hybrid nanoparticles reduced in vitro and in vivo premature release of ceramides and offer a viable platform for targeted delivery of lipophilic drugs. PMID:24065591
Large anti-HER2/neu liposomes for potential targeted intraperitoneal therapy of micrometastatic cancer
Sofou, Stavroula; Enmon, Richard; Palm, Stig; Kappel, Barry; Zanzonico, Pat; McDevitt, Michael R.; Scheinberg, David A.; Sgouros, George
Effective targeting and killing of intraperitoneally disseminated micrometastases remains a challenge. Objective/Methods In this work, we evaluated the potential of antibody-labeled PEGylated large liposomes as vehicles for direct intraperitoneal (i.p.) drug delivery with the aim to enhance the tumor-to-normal organ ratio and to improve the bioexposure of cancer cells to the delivered therapeutics while shifting the toxicities toward the spleen. These targeted liposomes are designed to combine: (1) specific targeting to and internalization by cancer cells mediated by liposome-conjugated tumor-specific antibodies, (2) slow clearance from the peritoneal cavity, and (3) shift of normal organ toxicities from the liver to the spleen due to their relatively large size. Results Conjugation of anti-HER2/neu antibodies to the surface of large (approximately 600 nm in diameter) PEGylated liposomes results in fast, specific binding of targeted liposomes to cancer cells in vitro, followed by considerable cellular internalization. In vivo, after i.p. administration, these liposomes exhibit fast, specific binding to i.p. cancerous tumors. Large liposomes are slowly cleared from the peritoneal cavity, and they exhibit increased uptake by the spleen relative to the liver, while targeted large liposomes demonstrate specific tumor uptake at early times. Although tissue and tumor uptake are greater for cationic liposomes, the tumor-to-liver and spleen-to-liver ratios are similar for both membrane compositions, suggesting a primary role for the liposome's size, compared to the liposome's surface charge. Conclusions The findings of this study suggest that large targeted liposomes administered i.p. could be a potent drug-delivery strategy for locoregional therapy of i.p. micrometastatic tumors. PMID:20070139
Electronic properties and morphology of Cu-phthalocyanine—C{sub 60} composite mixtures
Roth, Friedrich [Center for Free-Electron Laser Science/DESY, Notkestraße 85, D-22607 Hamburg (Germany); Lupulescu, Cosmin [Institute of Optics and Atomic Physics, TU Berlin, Straße des 17. Juni 135, D-10623 Berlin (Germany); Arion, Tiberiu [Center for Free-Electron Laser Science/DESY, Notkestraße 85, D-22607 Hamburg (Germany); Institut für Experimentalphysik, Universität Hamburg, Luruper Chaussee 149, D-22761 Hamburg (Germany); Darlatt, Erik; Gottwald, Alexander [Physikalisch-Technische Bundesanstalt (PTB), Abbestraße 2-12, D-10587 Berlin (Germany); Eberhardt, Wolfgang [Center for Free-Electron Laser Science/DESY, Notkestraße 85, D-22607 Hamburg (Germany); Institute of Optics and Atomic Physics, TU Berlin, Straße des 17. Juni 135, D-10623 Berlin (Germany)
Phthalocyanines in combination with C{sub 60} are benchmark materials for organic solar cells. Here, we have studied the morphology and electronic properties of co-deposited mixtures (blends) of these materials forming a bulk heterojunction as a function of the concentration of the two constituents. For a concentration of 1:1 of Cu-Phthalocyanine (CuPc):C{sub 60}, a phase separation into about 100?nm size domains is observed, which results in electronic properties similar to layered systems. For low C{sub 60} concentrations (10:1 CuPc:C{sub 60}), the morphology, as indicated by Low-Energy Electron Microscopy images, suggests a growth mode characterized by (amorphous) domains of CuPC, whereby the domain boundaries are decorated with C{sub 60}. Despite of these markedly different growth modes, the electronic properties of the heterojunction films are essentially unchanged.
Photophysical properties of zinc phthalocyanine-uridine single walled carbon nanotube - conjugates
NASA Astrophysics Data System (ADS)
Ogbodu, Racheal O.; Amuhaya, Edith K.; Mashazi, Philani; Nyokong, Tebello
The photophysical properties of the conjugate of uridine and zinc mono carboxy phenoxy phthalocyanine (ZnMCPPc-uridine, 4) are reported in this work. The conjugate was also adsorbed onto single walled carbon nanotubes (ZnMCPPc-uridine-SWCNT, 5). The X-ray photoelectron spectroscopy of 4 showed three N 1s peaks while that of 5 showed four N 1s peak, a new peak at 399.4 eV of 5 was assigned to pyrrolidonic nitrogen, due to the interaction of the pyrrolic nitrogen of 4 with the oxygen moiety of SWCNT-COOH in 5. The triplet lifetime, triplet and singlet oxygen quantum yields of the zinc mono carboxy phenoxy phthalocyanine increased by over 40% in the presence of uridine. SWCNTs resulted in only a small quenching of the triplet state parameters of 4.
Apoptosis induction by aluminum phthalocyanine tetrasulfonate-based sonodynamic therapy in HL-60 cells
NASA Astrophysics Data System (ADS)
Iwase, Yumiko; Yumita, Nagahiko; Nishi, Koji; Kuwahara, Hiroyuki; Fukai, Toshio; Ikeda, Toshihiko; Chen, Fu-shih; Momose, Yasunori; Umemura, Shin-ichiro
The present study aims to investigate sonodynamically-induced apoptosis using the phthalocyanine, chloroaluminum phthalocyanine tetrasulfonate (AlPcTS). HL-60 cells were exposed to ultrasound for up to 3 min in the absence and presence of AlPcTS. Apoptosis was analyzed by cell morphology, DNA fragmentation, and caspase-3 activity. Electron spin resonance was used to measure reactive oxygen species. The number of apoptotic cells showing membrane blebbing and cell shrinkage after combined treatment (ultrasound and AlPcTS) was significantly higher than following other treatments, including ultrasound alone and AlPcTS alone. Furthermore, DNA ladder formation, caspase-3 activation and enhanced nitroxide generation were observed in cells treated with ultrasound and AlPcTS. Sonodynamically induced apoptosis, caspase-3 activation, and nitroxide generation were significantly suppressed by histidine. The significant reduction by histidine indicated that ultrasonically generated reactive oxygen species, such as singlet oxygen, is an important mediator of sonodynamically-induced apoptosis.
Metallophthalocyanin-ocenes: scandium phthalocyanines with an ?(5)-bound Cp ring.
Platel, Rachel H; Teixeira Tasso, Thiago; Zhou, Wen; Furuyama, Taniyuki; Kobayashi, Nagao; Leznoff, Daniel B
A series of new scandium complexes supported by the phthalocyanine (Pc) ligand have been prepared and structurally characterized. Reaction of ScCl3 with phthalonitrile affords a mixture of PcScCl (1) and unreacted ScCl3, which upon addition of LiCH(SiMe3)2 yields THF-soluble PcSc(?-Cl2)Li(THF)2 (2). Metathesis with NaCp or LiCp* generates PcSc(?(5)-C5H5) and PcSc(?(5)-C5Me5), respectively, which represent the first examples of ?(5)-Cp metal phthalocyanines where the Cp fragment sandwiches the metal centre. PMID:25735598
Giant magnetocrystalline anisotropy of 5d transition metal-based phthalocyanine sheet.
Zhou, Jian; Wang, Qian; Sun, Qiang; Kawazoe, Yoshiyuki; Jena, Puru
Large magnetocrystalline anisotropy energy (MAE) is a critical requirement for nanomagnets for applications in magnetic memory and storage devices. Due to small spin-orbit interaction the MAE of ferromagnetic films or single molecule magnets based on 3d metals is small and in typical magnetic nanostructures it is of the order of 2-3 meV. We show that MAE as high as 140 meV can be achieved by applying an external electric field or a biaxial tensile strain to phthalocyanine sheets decorated by 5d transition metal atoms such as Os and Ir. Our observation is based on a systematic study of 5d transition metal absorbed ploy phthalocyanine (Pc) sheets using first-principles density functional theory (DFT) combined with self consistently determined Hubbard U that accounts for the strong correlation energy. We attribute the high MAE values to dxy and dx(2)-y(2) (dxz and dyz) interaction in Ir (Os) adsorbed structure. PMID:26073550
Electronic structure of a vapor-deposited metal-free phthalocyanine thin film
NASA Astrophysics Data System (ADS)
Alfredsson, Y.; Brena, B.; Nilson, K.; Ĺhlund, J.; Kjeldgaard, L.; Nyberg, M.; Luo, Y.; Mârtensson, N.; Sandell, A.; Puglia, C.; Siegbahn, H.
The electronic structure of a vapor-sublimated thin film of metal-free phthalocyanine (H2Pc) is studied experimentally and theoretically. An atom-specific picture of the occupied and unoccupied electronic states is obtained using x-ray-absorption spectroscopy (XAS), core- and valence-level x-ray photoelectron spectroscopy (XPS), and density-functional theory (DFT) calculations. The DFT calculations allow for an identification of the contributions from individual nitrogen atoms to the experimental N1s XAS and valence XPS spectra. This comprehensive study of metal-free phthalocyanine is relevant for the application of such molecules in molecular electronics and provides a solid foundation for identifying modifications in the electronic structure induced by various substituent groups.
Second- and third-order nonlinear properties of chiral phthalocyanine films
NASA Astrophysics Data System (ADS)
Muto, Tsuyoshi; Sassa, Takafumi; Aoyama, Tetsuya; Kimura, Mutsumi; Shirai, Hirofusa; Wada, Tatsuo
Vanadyl phthalocyanine derivatives having optically active side chains and the corresponding racemic isomers were synthesized and examined as nonlinear optical materials. These dyes were soluble in organic solvents and gave uniform thin films using spin coating. The thin films (neat or polymer doped) of each phthalocyanines showed the second- and third-order nonlinear optical responses under appropriate experimental conditions. The nonlinear optical susceptibilities of the optically active derivatives are larger than those of the corresponding racemic isomers. To clarify this enhancement phenomenon, we measured the electronic absorption- and circular dichloic spectra, and X-ray diffraction of the thin films. These results suggested that the optically active dyes forms one-dimensional columnar aggregates with one-handed helical sense and the columns further aligned into honeycomb-like chiral superstructures. It was surmised from the experimental results that the chiral superstructures enhance the nonlinear optical responses relative to the racemic analogues.
Influence of chlorine substitution on the self-assembly of zinc phthalocyanine.
Koudia, Mathieu; Abel, Mathieu; Maurel, Christian; Bliek, Ariane; Catalin, Daniel; Mossoyan, Mireille; Mossoyan, Jean-Charles; Porte, Louis
The adsorption and ordering of zinc phthalocyanine (ZnPc) and octachloro zinc phthalocyanine (ZnPcCl(8)) on an Ag(111) surface is studied in situ by scanning tunneling microscopy under ultrahigh vacuum. Two-dimensional self-assembled supramolecular domains are observed for these two molecules. We show how substituting chlorine atoms for half of the peripheral hydrogen atoms on ZnPc influences the self-assembly mechanisms. While intermolecular interactions are dominated by van der Waals forces in ZnPc molecular networks, ZnPcCl(8) molecular packing undergoes a sequential phase evolution driven by the creation of C-Cl...H-C hydrogen bonds between adjacent molecules. At the end of this evolution, the final molecular assembly involves all possible hydrogen bonds. Our study also reveals the influence of molecule-substrate interactions through the presence of fault lines generating a stripe structure in the molecular film. PMID:16706465
Phthalocyanine/chitosan-TiO2 photocatalysts: Characterization and photocatalytic activity
NASA Astrophysics Data System (ADS)
Hamdi, A.; Boufi, S.; Bouattour, S.
Chitosan (CS) was used as a template to prepare a hybrid chitosan-phthalocyanine-TiO2 (PC/CS-TiO2) photocatalyst at room temperature without any calcination treatment. The as-prepared hybrid photocatalyst (PC/CS-TiO2) was characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and UV-vis diffuse reflectance spectroscopy (DRS). The results of the photodegradation of aniline, used as a model pollutant, revealed that the hybrid photocatalyst (PC/CS-TiO2) exhibited a photocatalytic activity under visible-light irradiation. The enhanced activity of the hybrid catalyst is attributed to the cooperative role of the three components of the photocatalyst; chitosan as a template for the immobilization crystalline TiO2 nanoparticles, phthalocyanine that promote the light absorption in the visible range and TiO2 acting as an acceptor of electrons generated by the photons absorption to produce superoxide radicals.
Dimerization of titanyl phthalocyanine in thin films prepared by surface polymerization by ion-assisted deposition
Zachary, Adam M.; Drabik, Martin; Choi, Yongsoo; Bolotin, Igor L.; Biederman, Hynek; Hanley, Luke [Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607-7061 (United States); Faculty of Mathematics and Physics, Department of Macromolecular Physics, Charles University, Prague (Czech Republic); Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607-7061 (United States); Faculty of Mathematics and Physics, Department of Macromolecular Physics, Charles University, Prague (Czech Republic); Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607-7061 (United States)
Surface polymerization by ion-assisted deposition (SPIAD), the simultaneous dosing of hyperthermal ions while depositing an organic oligomer, was used to deposit titanyl phthalocyanine (TiOPc) thin films with 50 and 100 eV acetylene ions. The properties of the SPIAD TiOPc thin films are compared with films of the evaporated TiOPc monomer via examination of the electronic structure, ultraviolet-visible absorbance, and composition. Mass spectrometry, x-ray photoelectron spectroscopy, and other methods were used to determine the film composition, chemical bonding, and to examine the electronic structure. These results showed the formation of TiOPc dimers bound face to face. However, the overall phthalocyanine ring structure otherwise remained intact, except for small amounts of atmospheric oxidation at ion-induced radical sites.
Novel axially carborane-cage substituted silicon phthalocyanine photosensitizer; synthesis, characterization and photophysicochemical properties
NASA Astrophysics Data System (ADS)
Atmaca, Göknur Ya?a; Dizman, Cemil; Eren, Tar?k; Erdo?mu?, Ali
The novel axially dicarborane substituted silicon (IV) (SiPc-DC) phthalocyanine was synthesized by treating silicon phthalocyanine dichloride SiPc(Cl)2 (SiPc) with o-Carborane monool. The compound was characterized by mass spectrometry, UV-Vis, FT-IR, 1H and 11B Nuclear Magnetic Resonance Spectroscopy (NMR). Spectral, photophysical (fluorescence quantum yield) and photochemical (singlet oxygen (??) and photodegradation quantum yield (?d)) properties of the complex were reported in different solutions (Dimethyl sulfoxide (DMSO), Dimethylformamide (DMF) and Toluene). The results of spectral measurements showed that both SiPc and carborane cage can have potential to be used as sensitizers in photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) by their singlet oxygen efficiencies (?? = 0.41, 0.39).
First generation and trapping of a dehydrometallophthalocyanine starting from triazole-functionalized zinc phthalocyanine.
Vagin, Sergei I; Frickenschmidt, Antje; Kammerer, Bernd; Hanack, Michael
Direct 1N-amination of the triazole-fused zinc phthalocyanine 2 and oxidation of the formed amino derivative 3 resulted in the generation of the very reactive intermediate, the dehydrometallophthalocyanine 4, which was not known previously. The latter was trapped in situ with different dienes, for example, furan, tetraphenylcyclopentadienone, and anthracene to form the corresponding Diels-Alder adducts. The products were characterized by 1H and 13C-dept135 NMR, and UV/Vis spectroscopy, MALDI-TOF mass spectrometry, and elemental analysis, which are fully in agreement with their structure. The developed synthetic procedure opens a simple and versatile pathway towards unsymmetrical peripheral modification of phthalocyanines, which is readily applicable to the micromol scale and is important for the design of new interesting Pc-based systems. PMID:16106461
The interface between phthalocyanines and PEDOT:PSS: evidence for charge transfer and doping
NASA Astrophysics Data System (ADS)
Peisert, H.; Knupfer, M.; Zhang, F.; Petr, A.; Dunsch, L.; Fink, J.
As model systems, differently fluorinated representatives from the family of phthalocyanines (CuPC, CuPCF 4, and CuPCF 16) with different ionization potentials were evaporated onto PEDOT:PSS (mixture of poly-3,4-ethylenedioxy-thiophene (PEDOT) and polystyrenesulfonate (PSS)) thin films, which are often applied as electrode material in (all-)organic semiconductor devices. The electronic interface properties were studied using both core and valence level photoemission spectroscopy. The alignment of the electronic levels of the phthalocyanines on PEDOT:PSS is compared to inert and reactive inorganic substrates. For reactive systems, the direction of the charge transfer depends clearly on both the ionization potential of the organic semiconductor and the work function of the substrate.
Structural and electronic properties of porphyrins and phthalocyanines self assembled on conductive surfaces
NASA Astrophysics Data System (ADS)
Wiggins, Bryan Cortez
Phthalocyanine and porphyrin compounds are intensively studied for their important physical and electronic properties. These organic compounds possess semiconductor properties that make them great candidates for several thin film applications such as: photovoltaics devices, organic light emitted diodes (OLED), and sensors. Before these compound can be used to construct devices their structural and electronic properties at the molecular level must be understood. Scanning tunneling microscopy (STM) was used to investigate the geometrical structure of the aggregate and/or monolayer of the compound. X-ray photoelectron spectroscopy (XPS) studies show the chemical formation such as film composition and protonation state of nitrogens in the macrocycle ring. Ultraviolet photoelectron (UPS) and scanning tunneling spectroscopy, more specifically orbital mediated tunneling spectroscopy (OMTS) provided more insight into the electronic structure of these compounds. Three different compounds will be discussed in the following, diacid tetrasulfonatophenylporphine H2(H4TSPP), tetrakis (4-sulfonatophenyl) phthalocyanine (TSPc) and metal free naphthalocaynine (H2Nc).
Experimental and theoretical study of electronic structure of lutetium bi-phthalocyanine.
Bidermane, I; Lüder, J; Boudet, S; Zhang, T; Ahmadi, S; Grazioli, C; Bouvet, M; Rusz, J; Sanyal, B; Eriksson, O; Brena, B; Puglia, C; Witkowski, N
Using Near Edge X-Ray Absorption Fine Structure (NEXAFS) Spectroscopy, the thickness dependent formation of Lutetium Phthalocyanine (LuPc2) films on a stepped passivated Si(100)2×1 reconstructed surface was studied. Density functional theory (DFT) calculations were employed to gain detailed insights into the electronic structure. Photoelectron spectroscopy measurements have not revealed any noticeable interaction of LuPc2 with the H-passivated Si surface. The presented study can be considered to give a comprehensive description of the LuPc2 molecular electronic structure. The DFT calculations reveal the interaction of the two molecular rings with each other and with the metallic center forming new kinds of orbitals in between the phthalocyanine rings, which allows to better understand the experimentally obtained NEXAFS results. PMID:23802970
Enhanced Reverse Saturable Absorption and Optical Limiting in Heavy-Atom Substituted Phthalocyanines
NASA Technical Reports Server (NTRS)
Perry, J. W.; Mansour, K.; Marder, S. R.; Alvarez, D., Jr.; Perry, K. J.; Choong, I.
The reverse saturable absorption and optical limiting response of metal phthalocyaninies can be enhanced by using the heavy-atom effect. Phthalocyanines containing heavy metal atoms, such as In, Sn, and Pb show nearly a factor of two enhancement in the ratio of effective excited-state to ground-state absorption cross sections compared to those containing lighter atoms, such as Al and Si. In an f/8 optical geometry, homogeneous solutions of heavy metal phthalocyanines, at 30% linear transmission, limit 8-ns, 532-nm laser pulses to less than or equal to 3 (micro)J (the energy for 50% probability of eye damage) for incident pulses up to 800 (micro)J.
Role of buffer layer in electronic structures of iron phthalocyanine molecules on Au(111) This article has been downloaded from IOPscience. Please scroll down to see the full text article.
Gao, Hongjun
Role of buffer layer in electronic structures of iron phthalocyanine molecules on Au(111 layer in electronic structures of iron phthalocyanine molecules on Au(111) Sun Jia-Tao(), Pan Li layer on Au(111). Keywords: iron phthalocyanine, electronic structure calculations, buffer layer PACC
Aging of flat heterojunction zinc phthalocyanine\\/fullerene C 60 organic solar cells
R. Lessmann; Z. Hong; S. Scholz; B. Maennig; M. K. Riede; K. Leo
This work addresses the long-term aging of organic solar cells based on a flat zinc phthalocyanine (ZnPc)\\/C60 heterojunction. We investigate both the typical degradation behavior of the short circuit current and of the saturated photocurrent, defined as I(?1V). The latter remains constant after a relatively small initial decay, which is directly related to a substantial reduction of the contribution of
Dimerization of titanyl phthalocyanine in thin films prepared by surface polymerization by ion-assisted deposition
Adam M. Zachary; Martin Drabik; Yongsoo Choi; Igor L. Bolotin; Hynek Biederman; Luke Hanley
Surface polymerization by ion-assisted deposition (SPIAD), the simultaneous dosing of hyperthermal ions while depositing an organic oligomer, was used to deposit titanyl phthalocyanine (TiOPc) thin films with 50 and 100 eV acetylene ions. The properties of the SPIAD TiOPc thin films are compared with films of the evaporated TiOPc monomer via examination of the electronic structure, ultraviolet-visible absorbance, and composition.
Electrocatalytic Determination of Dithiocarbamate-Based Pesticides Using Electrodes Modified with Metal Phthalocyanines
L. G. Shaidarova; G. K. Budnikov; S. A. Zaripova
An electrocatalytic method has been proposed for determining dithiocarbamate-based pesticides (carbathion, nabam, ferbam, thiram, and thiuram) using a carbon-paste electrode modified with iron(II) and cobalt(II) phthalocyanines. The first wave of carbathion oxidation in both aqueous and organic solutions does not change compared to an unmodified carbon-paste electrode; for the second stage of oxidation, a decrease by 100 mV in the
Low-energy muon [LEM] study of Zn-phthalocyanine and ZnO thin films
H. V. Alberto; J. Piroto Duarte; A. Weidinger; R. C. Vilăo; J. M. Gil; N. Ayres de Campos; K. Fostiropoulos; T. Prokscha; A. Suter; E. Morenzoni
Implantation of low-energy muons in zinc-phthalocyanine (ZnPc) thin-films leads to the formation of muoniated radical states, the fast decaying of the ?SR signal at low fields being a clear indication of muonium formation. The formation probability of these paramagnetic states is independent of the implantation depth and amounts, as in the bulk, to approximately 100% of all muons. In these
Interdigitated Bulk Heterojunction Organic Photovoltaic Cells With Aligned Copper Phthalocyanine Nanorods
Ying Zheng; Robel Bekele; Jiaomin Ouyang; Jiangeng Xue
We show that vertically aligned nanorod arrays composed of copper phthalocyanine (CuPc) molecules can be grown on various substrates using the oblique angle deposition technique in high vacuum. High-density nanorod arrays with diameters of 20-70 nm and spacing of 10-100 nm have been achieved with either stationary or rotated substrates. Scanning electron and atomic force microscopies are combined to study
Nonenzymatic glucose biosensor based on overoxidized polypyrrole nanofiber electrode modified with cobalt(II) phthalocyanine tetrasulfonate
Levent Özcan; Yücel ?ahin; Hayrettin Türk
An enzymeless biosensor, based on electrodeposition of overoxidized polypyrrole nanofiber onto pencil graphite electrode and modified with cobalt(II) phthalocyanine tetrasulfonate (CoPcTS), was investigated in this study. CoPcTS showed electrocatalytic activity for the oxidation of glucose in alkaline solution. The electrochemical performance of the modified electrodes was investigated by differential pulse voltammetric (DPV) method. The resulting biosensor exhibited excellent performance for
The electric response behavior and microencapsulation of the pigment phthalocyanine green G using interfacial polymerization
Haiyan Mao; Chaoxia Wang; Chunxia Wang; Kairui Zhang; Shaohai Fu
The polyamide microcapsules for the electrophoretic display have been prepared via interfacial polymerization. The core material\\u000a of the microcapsules is electrophoretic fluid consisted of pigment phthalocyanine green G (CAS No. 1328-53-6) modified with\\u000a octadecylamine, tetrachloroethylene, and polyoxyethylene octylphenol ether (OP-10). The wall of the polyamide is synthesized\\u000a from paraphthaloyl chloride and diethylenetriamine. FT-IR indicated that octadecylamine was bonded to pigment
Optical and xerographic properties of phthalocyanine codeposited composite film and ultrathin multilayered structure
M. S. Xu; J. B. Xu; M. Wang; D. L. Que
The optical and xerographic properties of the phthalocyanine codeposited composite (cDC) films and ultrathin multilayered (UTML) structures have been studied. Observed UV-visible absorption spectra indicate that the Q-band absorption of the cDc films is different from that of the single component films, and from that of the UTML structures. The absorption peaks are shifted with the number and thickness of
Near-infrared sensitive small molecule organic photovoltaic cells based on chloroaluminum phthalocyanine
Rhonda F. Bailey-Salzman; Barry P. Rand; Stephen R. Forrest
The use of chloroaluminum phthalocyanine (ClAlPc) as a donor and C60 as an acceptor in planar double heterojunction organic photovoltaic cells with response extending into the near infrared is demonstrated. X-ray diffraction indicates that under the conditions used in this study ClAlPc grows as an amorphous film. Although the absorption and film morphology show no dependence on growth rate, device
Sensitivity of different cell lines to phototoxic effect of disulfonated chloroaluminium phthalocyanine
H. Kolarova; R. Lenobel; P. Kolar; M. Strnad
Photodynamic therapy (PDT) is a treatment for cancer involving three key components: sensitizer, light and tissue oxygen. A sensitizer is a chemical compound that can be excited by light of a specific wavelength. Phthalocyanine ClAlPcS2, belonging among the promising second generation of sensitizers, was evaluated as an inducer of photodamage on NIH3T3 (mouse fibroblasts), B16 (mouse melanoma), MCF7 (human breast
Oxygen electroreduction on multi-walled carbon nanotube supported metal phthalocyanines and porphyrins in alkaline media.
Kruusenberg, Ivar; Matisen, Leonard; Tammeveski, Kaido
Metal phthalocyanine and porphyrin modified electrodes were prepared using multi-walled carbon nanotubes (MWCNTs) as a support material. The catalyst materials were heat-treated before electrochemical testing. X-ray photoelectron spectroscopic study was carried out in order to examine the surface composition. The electroreduction of oxygen has been investigated on Fe phthalocyanine/MWCNT, Co phthalocyanine/MWCNT, Fe porphyrin/MWCNT and Co porphyrin/MWCNT catalysts. Electrochemical experiments were carried out in 0.1 M KOH employing the rotating disk electrode (RDE) method. The glassy carbon (GC) disk electrodes were modified with MN4 macrocycle/MWCNT catalysts using Tokuyama AS-4 ionomer. Electrochemical characterization of the materials showed that all the MN4 macrocycle/MWCNT modified GC electrodes are highly active for the reduction of oxygen in alkaline solutions. Particularly high electrocatalytic activity was observed for porphyrin-based electrodes heat-treated at 800 degrees C. The RDE results obtained are significant for the development of alkaline membrane fuel cells. PMID:23646786
Understanding domain symmetry in vanadium oxide phthalocyanine monolayers on Au (111)
NASA Astrophysics Data System (ADS)
Rochford, L. A.; Hancox, I.; Jones, T. S.
Understanding the growth of organic semiconductors on solid surfaces is of key importance for the field of organic electronics. Non planar phthalocyanines have shown great promise in organic photovoltaic (OPV) applications, but little of the fundamental surface characterization to understand their structure and properties has been performed. Acquiring a deeper understanding of the molecule/substrate interaction in small molecule systems is a vital step in controlling structure/property relationships. Here we characterize the vanadium oxide phthalocyanine (VOPc)/Au (111) surface using a combination of low energy electron diffraction (LEED) and scanning tunneling microscopy (STM), obtaining complex diffraction patterns which can be understood using two dimensional fast Fourier transform (2D-FFT) analysis of STM images. These measurements reveal coexistence of three symmetrically equivalent in-plane orientations with respect to the substrate, each of which is imaged simultaneously within a single area. Combining scanning probe and diffraction measurements allows symmetrically related domains to be visualized and structurally analyzed, providing fundamental information useful for the structural engineering of non-planar phthalocyanine interfaces.
Electronic absorption band broadening and surface roughening of phthalocyanine double layers by saturated solvent vapor treatment
Kim, Jinhyun [Department of Chemistry, Kookmin University, Seoul 136-702 (Korea, Republic of)] [Department of Chemistry, Kookmin University, Seoul 136-702 (Korea, Republic of); Yim, Sanggyu, E-mail: firstname.lastname@example.com [Department of Chemistry, Kookmin University, Seoul 136-702 (Korea, Republic of)] [Department of Chemistry, Kookmin University, Seoul 136-702 (Korea, Republic of)
Variations in the electronic absorption (EA) and surface morphology of three types of phthalocyanine (Pc) thin film systems, i.e. copper phthalocyanine (CuPc) single layer, zinc phthalocyanine (ZnPc) single layer, and ZnPc on CuPc (CuPc/ZnPc) double layer film, treated with saturated acetone vapor were investigated. For the treated CuPc single layer film, the surface roughness slightly increased and bundles of nanorods were formed, while the EA varied little. In contrast, for the ZnPc single layer film, the relatively high solubility of ZnPc led to a considerable shift in the absorption bands as well as a large increase in the surface roughness and formation of long and wide nano-beams, indicating a part of the ZnPc molecules dissolved in acetone, which altered their molecular stacking. For the CuPc/ZnPc film, the saturated acetone vapor treatment resulted in morphological changes in mainly the upper ZnPc layer due to the significantly low solubility of the underlying CuPc layer. The treatment also broadened the EA band, which involved a combination of unchanged CuPc and changed ZnPc absorption.
Controlling Morphology and Molecular Packing of Alkane Substituted Phthalocyanine Blend Bulk Heterojunction Solar Cells†
Jurow, Matthew J.; Hageman, Brian A.; Nam, Chang-Yong; Pabon, Cesar; Black, Charles T.
Systematic changes in the exocyclic substiution of core phthalocyanine platform tune the absorption properties to yield commercially viable dyes that function as the primary light absorbers in organic bulk heterojunction solar cells. Blends of these complementary phthalocyanines absorb a broader portion of the solar spectrum compared to a single dye, thereby increasing solar cell performance. We correlate grazing incidence small angle x-ray scattering structural data with solar cell performance to elucidate the role of nanomorphology of active layers composed of blends of phthalocyanines and a fullerene derivative. A highly reproducible device architecture is used to assure accuracy and is relevant to films for solar windows in urban settings. We demonstrate that the number and structure of the exocyclic motifs dictate phase formation, hierarchical organization, and nanostructure, thus can be employed to tailor active layer morphology to enhance exciton dissociation and charge collection efficiencies in the photovoltaic devices. These studies reveal that disordered films make better solar cells, short alkanes increase the optical density of the active layer, and branched alkanes inhibit unproductive homogeneous molecular alignment. PMID:23589766
The antimicrobial activity of liposomal lauric acids against Propionibacterium acnes
Darren Yang; Dissaya Pornpattananangkul; Teruaki Nakatsuji; Michael Chan; Dennis Carson; Chun-Ming Huang; Liangfang Zhang
This study evaluated the antimicrobial activity of lauric acid (LA) and its liposomal derivatives against Propionibacterium acnes (P. acnes), the bacterium that promotes inflammatory acne. First, the antimicrobial study of three free fatty acids (lauric acid, palmitic acid and oleic acid) demonstrated that LA gives the strongest bactericidal activity against P. acnes. However, a setback of using LA as a
Functionalization of liposomes: microscopical methods for preformulative screening.
Belletti, Daniela; Vandelli, Maria Angela; Tonelli, Massimo; Zapparoli, Mauro; Forni, Flavio; Tosi, Giovanni; Ruozi, Barbara
Abstract The development of smart delivery systems able to deliver and target a drug to the site of action is one of the major challenges in the field of pharmaceutical technology. The surface modification of nanocarriers, such as liposomes, is widely investigated either for increasing the blood circulation time (by pegylation) or for interacting with specific tissues or cells (by conjugation of a selective ligand as a monoclonal antibody, mAb). Microscopical analysis thereby is a useful approach to evaluate the morphology and the size owing to resolution and versatility in defining either surface modification or the architecture and the internal structure of liposomes. This contribution aims to connect the outputs obtained by transmission electron (TEM) and atomic force (AFM) microscopical techniques for identifying the modifications on the liposomal surface. To reach this objective, we prepared liposomes applying two different pegylation technologies and further modifying the surface by mAb conjugation. This work demonstrates the feasibility to apply the combined approach (TEM and AFM analysis) in the evaluation of the efficacy of a surface engineering process. PMID:25203607
Ex vivo liposome-mediated gene transfer to lung isografts
Carlos H. Boasquevisque; Bassem N. Mora; Matthew Bernstein; William O. Osburn; Jennifer Nietupski; Ronald K. Scheule; Joel D. Cooper; Mitchell Botney; G. Alexander Patterson
Objective: Gene therapy is a promising strategy to modify ischemia-reperfusion injury and rejection after transplantation. We evaluated variables that may affect ex vivo gene transfer to rat lung isografts. Methods: Left lungs were harvested and perfused via the pulmonary vein with chloramphenicol acetyltransferase complementary deoxyribonucleic acid complexed with cationic liposomes. Several variables were examined: (1) Influence of temperature: In group
Interaction of curcumin with lipid monolayers and liposomal bilayers
Anna Karewicz; Dorota Bielska; Barbara Gzyl-Malcher; Mariusz Kepczynski; Rados?aw Lach; Maria Nowakowska
Curcumin shows huge potential as an anticancer and anti-inflammatory agent. However, to achieve a satisfactory bioavailability and stability of this compound, its liposomal form is preferable. Our detailed studies on the curcumin interaction with lipid membranes are aimed to obtain better understanding of the mechanism and eventually to improve the efficiency of curcumin delivery to cells. Egg yolk phosphatidylcholine (EYPC)
[Transcorneal drug delivery: prospects for the use of liposomes].
Aliautdin, R N; Iezhitsa, I N; Agarval, R
Anatomical and physiological ocular surface barriers are responsible for low bioavailability of topical ophthalmic drugs. The unique structure of the cornea, epithelial cells and hydrophilic stroma in particular, impedes permeation of hydro- and lipophilic drugs via common routs of administration. The tear film with its proteins and enzymes also acts as a barrier. Despite several corneal transporters that take part in permeation of some drugs, increasing bioavailability of ophthalmic drugs in general remains a question of current importance. Liposomes are an option. These vesicular structures consist of the outer lipid bilayer and the inner aqueous compartment, which can be filled with a medication solution. This peculiarity of liposomes ensures their penetration through both hydro- and lipophilic mediums of the eye, including the barriers of the anterior and posterior segments. Liposomes are effective means of vectored drug delivery into the anterior chamber. This paper presents a review of the current knowledge on the interaction of drugs and ocular surface barriers as well as the prospects for the use of liposomes for transcorneal drug delivery. PMID:25306734
Improvements of cellular stress response on resveratrol in liposomes
Julijana Kristl; Karmen Teska?; Carla Caddeo; Zrinka Abramovi?; Marjeta Šentjurc
Resveratrol (RSV) has proven potential in prophylaxis and treatment of various disorders mediated by free radicals and oxidative stress. RSV solubility, stability, and cytotoxicity must be regulated for satisfactory bioavailability. Here, RSV was loaded into liposomes, characterized by PCS and TEM and evaluated on HEK293 cell line by metabolic activity assay, electron paramagnetic resonance, and fluorescence microscopy.RSV at 10?M induced
Liposome-based approaches to overcome anticancer drug resistance
Christoph Mamot; Daryl C. Drummond; Keelung Hong; Dmitri B. Kirpotin; John W. Park
Drug resistance remains an important obstacle towards better outcomes in the treatment of cancer. One general approach to overcome this problem has been to inhibit specific resistance mechanisms, such as P-glycoprotein (PGP)-mediated drug efflux, using small molecule agents or other therapeutic strategies. Alternatively, drug delivery approaches using liposomes or other carriers can in principle target drugs to tumor tissue, tumor
Targeting Cancer with Bugs and Liposomes: Ready, Aim, Fire
Ian Cheong; Xin Huang; Luis A. Diaz; Shibin Zhou
One of the major challenges facing cancer therapy today is achieving specificity. Current efforts to meet this challenge are focused on developing targeted therapeutics specific to the cancer cell. An alternative approach is to selectively deliver cytotoxic agents to the tumor site. With this end in mind, liposomes optimized for physical robustness have been developed and used clinically as drug
Chiral recognition of bilirubin and biliverdin in liposomes and micelles.
Novotná, Pavlína; Králík, František; Urbanová, Marie
The structural formula of biologically important chiral pigments bilirubin and biliverdin differs only by one double bond. We showed that this results in dissimilar interactions with two models of membranes: cationic liposomes composed of 3?-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol and zwitterionic micelles from 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). While the liposomes recognized the P-form of bilirubin, the micelles recognized its M-form. Both recognized the P-form of biliverdin. Our study also comprised ternary systems consisting of the pigments, model membranes and serum albumin (human and bovine). Bilirubin preferentially interacted with the albumins even in the presence of the liposomes. On the other hand, biliverdin preferred the liposomes. Remarkably, the presence of CHAPS completely changed the biliverdin binding to the protein. Because our study was oriented on different chiral interactions, a chiroptical method of electronic circular dichroism was chosen as the principal method to study our systems. As complementary methods, UV-vis absorption and fluorescence emission were used. PMID:26071845
Liposomal bupivacaine: a review of a new bupivacaine formulation.
Chahar, Praveen; Cummings, Kenneth C
Many attempts have been made to increase the duration of local anesthetic action. One avenue of investigation has focused on encapsulating local anesthetics within carrier molecules to increase their residence time at the site of action. This article aims to review the literature surrounding the recently approved formulation of bupivacaine, which consists of bupivacaine loaded in multivesicular liposomes. This preparation increases the duration of local anesthetic action by slow release from the liposome and delays the peak plasma concentration when compared to plain bupivacaine administration. Liposomal bupivacaine has been approved by the US Food and Drug Administration for local infiltration for pain relief after bunionectomy and hemorrhoidectomy. Studies have shown it to be an effective tool for postoperative pain relief with opioid sparing effects and it has also been found to have an acceptable adverse effect profile. Its kinetics are favorable even in patients with moderate hepatic impairment, and it has been found not to delay wound healing after orthopedic surgery. More studies are needed to establish its safety and efficacy for use via intrathecal, epidural, or perineural routes. In conclusion, liposomal bupivacaine is effective for treating postoperative pain when used via local infiltration when compared to placebo with a prolonged duration of action, predictable kinetics, and an acceptable side effect profile. However, more adequately powered trials are needed to establish its superiority over plain bupivacaine. PMID:23049275
Single cell targeting using plasmon resonant gold-coated liposomes
NASA Astrophysics Data System (ADS)
Leung, Sarah J.; Romanowski, Marek
We have developed an experimental system with the potential for the delivery and localized release of an encapsulated agent with high spatial and temporal resolution. We previously introduced liposome-supported plasmon resonant gold nanoshells; in this composite structure, the liposome allows for the encapsulation of substances, such as therapeutic agents, neurotransmitters, or growth factors, and the plasmon resonant structure facilitates the rapid release of encapsulated contents upon laser light illumination. More recently, we demonstrated that these gold-coated liposomes are capable of releasing their contents in a spectrally-controlled manner, where plasmon resonant nanoparticles only release content upon illumination with a wavelength of light matching their plasmon resonance band. We now show that this release mechanism can be used in a biological setting to deliver a peptide derivative of cholecystokinin to HEK293 cells overexpressing the CCK2 receptor. Using directed laser light, we may enable localized release from gold-coated liposomes to enable accurate perturbation of cellular functions in response to released compounds; this system may have possible applications in signaling pathways and drug discovery.
Mucoadhesive liposomes as new formulation for vaginal delivery of curcumin.
Berginc, Katja; Suljakovi?, Sabina; Škalko-Basnet, Nataša; Kristl, Albin
Local delivery to the affected area represents the optimal means by which advantageous pharmacological properties of curcumin may be fully exploited as currently, due to the biopharmaceutical limitations associated with this polyphenol, its full beneficial effects remain limited. Curcumin-containing liposomes coated with bioadhesive polymers of natural and synthetic origin (chitosan and Carbopol) were evaluated in vitro. For these purposes, an in vitro model of vaginal mucus was developed allowing the monitoring of curcumin permeability in the conditions mimicking vaginal environment. The model was optimized by varying the amounts of glycoproteins, as compared to the permeabilities determined through isolated bovine mucus. The strength of bioadhesion was evaluated using the isolated bovine mucosa. Both curcumin solution and non-coated curcumin liposomes served as controls. Bioadhesive polymers enabled significantly higher (p<0.05) curcumin permeability through the artificial and isolated bovine mucus compared to the controls. Polymer coating of liposomes resulted in an increase in their bioadhesiveness. Mucoadhesive liposomes can be considered as potential novel drug delivery systems intended for vaginal administration of curcumin. PMID:24534774
Three model shapes of Doxorubicin for liposome encapsulation.
Sumetpipat, Kanes; Baowan, Duangkamon
Targeted drug delivery provides a possible method for the transfer of drug molecules into cancer cells. Liposomes together with a drug, such as Doxorubicin (DOX) inside the liposomes, can be formed as a nano-capsule. In this study, we are interested in finding a favorable size of liposome and an appropriate shape of DOX cluster: sphere, cylinder or ellipsoid. Using mathematical modeling, the interaction energy of the system is obtained from the Lennard-Jones potential and the continuum assumption which assumes that discrete atomic structure can be replaced by an average atomic density spread over a surface. The numerical results show that the spherical shape gives the lowest energy at the equilibrium configuration amongst the three shapes. In the case of equivalent surface areas, the spherical shape gives the energy lower than -4,000 kJ/mol at the equilibrium while the energies for the other cases do not come close to this level. Further in the case of a liposome of 50 nm in radius, the sphere of radius 49.726 nm, equivalent to 31,072 nm(2) surface area, gives the minimum energy at -6,642 kJ/mol. However, an equivalent cylindrical shape is not possible due to geometric constraints. The lowest minimum energy for the ellipsoid occurs for equal major and minor axes, namely for the spherical case. The results presented here are a first step in the design and implementation of a drug molecule for a targeted drug delivery system. PMID:25374391
Association between cationic liposomes and low molecular weight hyaluronic acid.
Gasperini, Antonio A M; Puentes-Martinez, Ximena E; Balbino, Tiago Albertini; Rigoletto, Thais de Paula; Corręa, Gabriela de Sá Cavalcanti; Cassago, Alexandre; Portugal, Rodrigo Villares; de La Torre, Lucimara Gaziola; Cavalcanti, Leide P
This work presents a study of the association between low molecular weight hyaluronic acid (16 kDa HA) and cationic liposomes composed of egg phosphatidylcholine (EPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). The cationic liposome/HA complexes were evaluated to determine their mesoscopic structure, average size, zeta potential, and morphology as a function of the amount of HA in the system. Small angle X-ray scattering results revealed that neighboring cationic liposomes either stick together after a partial coating of low concentration HA or disperse completely in excess of HA, but they never assemble as multilamellar vesicles. Cryo-transmission electron microscopy images confirm the existence of unilamellar vesicles and large aggregates of unilamellar vesicles for HA fractions up to 80% (w/w). High concentrations of HA (> 20% w/w) proved to be efficient for coating extruded liposomes, leading to particle complexes with sizes in the nanoscale range and a negative zeta potential. PMID:25730494
Biocompatible anionic polyelectrolyte for improved liposome based gene transfection.
Chen, Ming; Zeng, Zhiying; Qu, Xiaohuan; Tang, Yaqin; Long, Qipeng; Feng, Xuli
Cationic liposomes have been widely used as efficient gene carriers. However, the serious cytotoxicity caused by exposed positive charges restricts the further application of those kinds of gene vectors. Thus, it is challenging to develop biocompatiable non-positive charge carriers to achieve high gene transfection efficiencies. Herein, we report a novel design by pasting biocompatible anionic polyelectrolyte, namely alginic acid, hyaluronic acid, pectin and polyglutamic acid, to the positive charge surface of liposome/pDNA complex. Through shielding the positive charges, the new gene carriers show decreased cytotoxicity while still maintaining high transfection efficiency. To be noted, the complex formed by coating polyglutamic acid to the surface of liposome/pDNA greatly enhanced the transfection efficiency in HepG2 cells, and the use of pectin shows increased transfection in MCF-7 cells. Hemolysis assay proved a possible mechanism that when the new gene complex was internalized into cells, as acidity increases, more side chains become hydrophobic, and thus destabilizing the endosomal membrane to accelerate DNA escape. The present results suggest that such anionic polyelectrolyte covered liposome based carrier possess promising application for clinical gene delivery. PMID:26004001
LeciPlex, invasomes, and liposomes: A skin penetration study.
Shah, Sanket M; Ashtikar, Mukul; Jain, Ankitkumar S; Makhija, Dinesh T; Nikam, Yuvraj; Gude, Rajiv P; Steiniger, Frank; Jagtap, Aarti A; Nagarsenker, Mangal S; Fahr, Alfred
The present study compares three vesicular systems, cationic LeciPlex, invasomes, and conventional liposomes for their ability to deliver drugs deep into the skin. Skin penetration ability of the three vesicular systems was studied for two drugs namely idebenone (antioxidant/anticancer) and azelaic acid (antiacne). All systems showed sizes in nanometer range with small polydispersity indices. Vesicular systems were characterized by CryoTEM studies to understand the differences in morphology of the vesicular systems. Ex vivo human skin penetration studies suggested a pattern in penetration of drugs in different layers of the skin: LeciPlex showed higher penetration for idebenone whereas invasomes showed higher penetration of azelaic acid. Ex vivo study using a fluorescent dye (DiI) was performed to understand the differences in the penetration behavior of the three vesicular systems on excised human skin. In vitro cytotoxicity studies on B16F10 melanoma cell lines revealed, when loaded with idebenone, LeciPlex formulations had the superior activity followed by invasomes and liposomes. In vitro antimicrobial study of azelaic acid loaded systems on Propionibacterium acne revealed high antimicrobial activity for DDAB leciplex followed by almost equal activity for invasomes and CTAB LeciPlex followed by liposomes. Whereas antiacne efficacy study in rats for azelaic acid loaded systems, invasomes exhibited the best antiacne efficacy followed by liposomes and LeciPlex. PMID:26002568
Liposomal bupivacaine: a review of a new bupivacaine formulation
Chahar, Praveen; Cummings, Kenneth C
Many attempts have been made to increase the duration of local anesthetic action. One avenue of investigation has focused on encapsulating local anesthetics within carrier molecules to increase their residence time at the site of action. This article aims to review the literature surrounding the recently approved formulation of bupivacaine, which consists of bupivacaine loaded in multivesicular liposomes. This preparation increases the duration of local anesthetic action by slow release from the liposome and delays the peak plasma concentration when compared to plain bupivacaine administration. Liposomal bupivacaine has been approved by the US Food and Drug Administration for local infiltration for pain relief after bunionectomy and hemorrhoidectomy. Studies have shown it to be an effective tool for postoperative pain relief with opioid sparing effects and it has also been found to have an acceptable adverse effect profile. Its kinetics are favorable even in patients with moderate hepatic impairment, and it has been found not to delay wound healing after orthopedic surgery. More studies are needed to establish its safety and efficacy for use via intrathecal, epidural, or perineural routes. In conclusion, liposomal bupivacaine is effective for treating postoperative pain when used via local infiltration when compared to placebo with a prolonged duration of action, predictable kinetics, and an acceptable side effect profile. However, more adequately powered trials are needed to establish its superiority over plain bupivacaine. PMID:23049275
Effect of liposomes and niosomes on skin permeation of enoxacin
Jia-You Fang; Chi-Tzong Hong; Wen-Ta Chiu; Ying-Yue Wang
The skin permeation and partitioning of a fluorinated quinolone antibacterial agent, enoxacin, in liposomes and niosomes, after topical application, were elucidated in the present study. In vitro percutaneous absorption experi- ments were performed on nude mouse skin with Franz diffusion cells. The influence of vesicles on the physicochemical property and stability of the formulations were measured. The enhanced delivery across
Partition of sodium dodecyl sulfate into stratum corneum lipid liposomes
D. T. Downing; W. Abraham; B. K. Wegner; K. W. Willman; J. L. Marshall
Synthetic detergents produce deleterious effects on human skin as the result of being taken up by the stratum corneum (SC). The present study aimed to determine to what extent a typical detergent enters the SC lipid lamellae, and what effect this might have on the physical properties of the lipids. These effects were studied in large unilamellar liposomes prepared from
pH-sensitive liposomes: characterization and application
Connor, J.
It has been demonstrated that liposomes composed of dioleoylphosphatidylethanolamine (DOPE) and palmitoylhomocysteine (PHC) have the ability to fuse with adjacent membranes upon exposure to mildly acid pH. The ability of liposomes to fuse is absolutely dependent on the presence of DOPE and a weakly acidic amphiphile. The acid induced fusion event is a leaky process, but the leakage can be reduced by 50%, with only a small loss of fusion ability, by the inclusion of 40 mole percent cholesterol. Using an established monoclonal antibody targeting system. pH-sensitive immunoliposomes were prepared which successfully delivered entrapped calcein to the cytoplasm of target cells. The addition of chloroquine, which raises the internal pH of cellular vacuoles, blocks the cytoplasmic delivery of the pH-sensitive immunoliposomes. pH-insensitive immunoliposomes delivered calcein only to the endosome/lysosome system and not the cytoplasm. /sup 31/P-NMR and light scattering of DOPE:OA liposomes under acidic conditions demonstrate that the effect of the protons and the divalent cations is to force the DOPE to revert to the hexagonal II configuration. In vivo experiments with DOPE:OA immunoliposomes indicate that the liposomes rapidly aggregate and release their contents upon exposure to plasma. These results indicate that pH-sensitive immunoliposomes are an effective tool for in vitro cytoplasmic delivery but are ineffective for in vivo delivery at this point in development.
Topical liposome delivery of molecules to hair follicles in mice
Lingna Li; Robert M. Hoffman
The hair cycle consisting of growing and resting phases, is subject to widespread disease such as androgenic alopecia or loss of pigment which are in need of effective, targeted therapeutics. In order to develop a hair-follicle delivery system we demonstrate here that phosphatidylcholine liposomes entrapping either the fluorescent dye calcein or the pigment melanin can deliver these molecules into the
Lead Ions Encapsulated in Liposomes and Their Effect on Staphylococcus aureus
Kensova, Renata; Blazkova, Iva; Konecna, Marie; Kopel, Pavel; Chudobova, Dagmar; Zitka, Ondrej; Vaculovicova, Marketa; Hynek, David; Adam, Vojtech; Beklova, Miroslava; Kizek, Rene
The aim of the study was the preparation of a liposome complex with encapsulated lead ions, which were electrochemically detected. In particular, experiments were focused on the potential of using an electrochemical method for the determination of free and liposome-encapsulated lead and determination of the encapsulation efficiency preventing the lead toxicity. Primarily, encapsulation of lead ions in liposomes and confirmation of successful encapsulation by electrochemical methods was done. Further, the reduction effect of the liposome matrix on the detected electrochemical signal was monitored. Besides encapsulation itself, comparison of toxicity of free lead ions and lead ions encapsulated in liposome was tested. The calculated IC50 values for evaluating the lead cytotoxicity showed significant differences between the lead enclosed in liposomes (28 µM) and free lead ions (237 µM). From the cytotoxicity studies on the bacterial strain of S. aureus it was observed that the free lead ions are less toxic in comparison with lead encapsulated in liposomes. Liposomes appear to be a suitable carrier of various substances through the inner cavity. Due to the liposome structure the lead enclosed in the liposome is more easily accepted into the cell structure and the toxicity of the enclosed lead is higher in comparison to free lead ions. PMID:24317385
Influence of curcumin-loaded cationic liposome on anticancer activity for cervical cancer therapy.
Saengkrit, Nattika; Saesoo, Somsak; Srinuanchai, Wanwisa; Phunpee, Sarunya; Ruktanonchai, Uracha Rungsardthong
The delivery of curcumin has been explored in the form of liposomal nanoparticles to treat various cancer cells. Since curcumin is water insoluble and an effective delivery route is through encapsulation in liposomes, which were modified with three components of DDAB, cholesterol and non-ionic surfactant. The purpose of this study was to establish a critical role of DDAB in liposomes containing curcumin at cellular response against two types of cell lines (HeLa and SiHa). Here, we demonstrate that DDAB is a potent inducer of cell uptake and cell death in both cell lines. The enhanced cell uptake was found on DDAB-containing liposome, but not on DDAB-free liposome. However, the cytotoxicity of DDAB-containing liposomes was high and needs to be optimized. The cytotoxicity of liposomal curcumin was more pronounced than free curcumin in both cells, suggesting the benefits of using nanocarrier. In addition, the anticancer efficiency and apoptosis effect of the liposomal curcumin formulations with DDAB was higher than those of DDAB-free liposomes. Therefore curcumin loaded liposomes indicate significant potential as delivery vehicles for the treatment of cervical cancers. PMID:24246195
Doxorubicin liposomes as an investigative model to study the skin permeation of nanocarriers.
Boakye, Cedar H A; Patel, Ketan; Singh, Mandip
The objectives of this study were to develop an innovative investigative model using doxorubicin as a fluorophore to evaluate the skin permeation of nanocarriers and the impact of size and surface characteristics on their permeability. Different doxorubicin-loaded liposomes with mean particle size <130nm and different surface chemistry were prepared by ammonium acetate gradient method using DPPC, DOPE, Cholesterol, DSPE-PEG 2000 and 1,1-Di-((Z)-octadec-9-en-1-yl) pyrrolidin-1-ium chloride (CY5)/DOTAP/1,2-dioleoyl-sn-glycero-3-phosphate (DOPA) as the charge modifier. There was minimal release of doxorubicin from the liposomes up to 8h; indicating that fluorescence observed within the skin layers was due to the intact liposomes. Liposomes with particle sizes >600nm were restricted within the stratum corneum. DOTAP (p<0.01) and CY5 (p<0.05) liposomes demonstrated significant permeation into the skin than DOPA and PEG liposomes. Tape stripping significantly (p<0.01) enhanced the skin permeation of doxorubicin liposomes but TAT-decorated doxorubicin liposomes permeated better (p<0.005). Blockage of the hair follicles resulted in significant reduction in the extent and intensity of fluorescence observed within the skin layers. Overall, doxorubicin liposomes proved to be an ideal fluorophore-based model. The hair follicles were the major route utilized by the liposomes to permeate skin. Surface charge and particle size played vital roles in the extent of permeation. PMID:25910414
Pirfenidone-loaded liposomes for lung targeting: preparation and in vitro/in vivo evaluation
Meng, Hui; Xu, Yong
Background The purpose of this study was to develop novel pirfenidone (PFD)-loaded liposomes for targeting to the lung. Methods The liposomes were prepared by the film hydration method, and their in vitro/vivo characteristics were evaluated. Results The PFD liposomes appeared visually as green to yellowish suspensions and were spherical in shape. The particle size was 582.3±21.6 nm and the entrapment efficiency was relatively high (87.2%±5.7%). The liposomes showed typical sustained and prolonged drug-release behavior in vitro and fitted well with the Weibull distribution equation. The relatively slower time taken to reach a minimal plasma PFD concentration in vivo suggests that PFD liposomes have a sustained-release profile, which is consistent with the results of the in vitro release study. The PFD liposomes showed the largest area under the curve for the lung. The high distribution of PFD achieved in the lungs using this liposomal formulation may be explained by physical entrapment of the liposomes in the vascular network of the lung. Histopathological results indicated that liposomal PFD could alleviate pathological injury in lung tissue. Conclusion This liposomal formulation can enable sustained release of PFD and increase targeting to the lung. PMID:26185416
Bisphosphonate-derivatized liposomes to control drug release from collagen/hydroxyapatite scaffolds.
Wang, Guilin; Babada?li, Mustafa Ege; Uluda?, Hasan
A drug delivery system was developed by combining composite scaffolds made up of collagen and hydroxyapatite (Col/HA) with bisphosphonate (BP)-derivatized liposomes. The Col/HA scaffold was prepared by a freeze-drying method to yield a porous scaffold. The liposomes were composed of distearoylphosphocholine, cholesterol, distearoylphosphoethanolamine-poly(ethylene glycol) (DSPE-PEG), and a bone-binding bisphosphonate (BP) attached to the DSPE-PEG (DSPE-PEG-BP). By taking advantage of the specific interaction between the liposomal BP and the HA incorporated into the scaffold, the BP-decorated liposomes (BP-liposomes) were shown to display a strong affinity to Col/HA scaffolds. Three different model drugs, carboxyfluorescein (CF), doxorubicin (DOX), and lysozyme (LYZ) were entrapped in liposomes; there were no differences in drug release from the liposomes whether the liposomes were BP decorated or not. Whereas unencapsulated drugs and drugs encapsulated in PEG-liposomes displayed rapid release from the scaffolds, the drugs entrapped in BP-liposomes showed a slower release from the Col/HA scaffolds. We conclude that the proposed system can prolong the in situ residence of model drugs and has the potential to provide a sustained drug release platform in bone regeneration and repair. PMID:21557579
A targeting drug-delivery model via interactions among cells and liposomes under ultrasonic excitation
NASA Astrophysics Data System (ADS)
Xi, Xiaoyu; Yang, Fang; Chen, Di; Luo, Yi; Zhang, Dong; Gu, Ning; Wu, Junru
In our previous work, it was found that acoustic cavitation might play a role in improving the cell permeability to microparticles when liposomes were used in an in vitro experiment. The purpose of this project is to expand our study and to learn other possible mechanisms by which cells may interact with liposomes under ultrasound (US) excitation and become transiently permeable to microparticles. It is further hypothesized that two possible scenarios may be involved in in vitro experiments: (1) drug-carrying liposomes transiently overcome the cell membrane barrier and enter into a cell while the cell is still viable; (2) the liposomes incorporate with a cell at its membrane through a fusing process. To prove this hypothesis, liposomes of two different structures were synthesized: one has fluorescent molecules encapsulated into liposomes and the other has fluorescent markers incorporated into the shells of liposomes. Liposomes of each kind were mixed with human breast cancer cells (MCF7-cell line) in a suspension at 5 (liposomes) : 1 (cell) ratio and were then exposed to a focused 1 MHz ultrasound beam at its focal region for 40 s. The US signal contained 20 cycles per tone-burst at a pulse-repetition-frequency of 10 kHz; the spatial peak acoustic pressure amplitude was 0.25 MPa. It was found that the possible mechanisms might include the acoustic cavitation, the endocytosis and cell-fusion. Acoustic radiation force might make liposomes collide with cells effectively and facilitate the delivery process.
Lymph node localization of non-specific antibody-coated liposomes
Mangat, S.; Patel, H.M.
Subcutaneously injected small unilamellar liposomes are drained into the lymphatics and localized in the regional lymph nodes, and thus they can be used for the detection of metastatic spread in breast cancer patients and for delivery of drugs to diseased lymph nodes. An aqueous phase marker, (/sup 125/I)-polyvinylpyrrolidone, and a lipid phase marker, (/sup 3/H)-cholesterol, were used to study the lymph node localization of IgG-coated liposomes injected subcutaneously into mouse and rat footpads. The results show that human immunoglobulin G (IgG) coated liposomes are rapidly removed from the site of injection and are localized in the regional lymph nodes to a greater extent than control liposomes (i.e. liposomes without IgG). Free IgG was found to inhibit the uptake of IgG-coated liposomes by the lymph nodes. The localization of IgG-coated liposomes in the regional lymph nodes is influenced by charge of the liposomes. The results presented here suggest that antibody-coated liposomes may provide a more efficient way of delivering therapeutic agents to the lymph nodes in the treatment of diseases such as breast cancer with lymph node involvement. Similarly, monoclonal antibody-coated liposomes containing lymphoscintigraphic material may improve the detection of lymph node metastases. 26 references, 3 figures, 3 tables.
Vitamin E TPGS coated liposomes enhanced cellular uptake and cytotoxicity of docetaxel in brain cancer cells.
Muthu, Madaswamy S; Kulkarni, Sneha A; Xiong, Jiaqing; Feng, Si-Shen
The aim of this work was to develop a drug delivery system of liposomes, which are coated with D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), a PEGylated vitamin E, with docetaxel as a model drug for enhanced treatment of brain tumour in comparison with the nude liposomes as well as with the so-called stealth liposomes, i.e. those coated with polyethylene glycol (PEG), which have been intensive investigated in the literature. Docetaxel or coumarin-6 loaded liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta potential and drug encapsulation efficiency. C6 glioma cells were employed as an in vitro model to access cellular uptake and cytotoxicity of the drug or coumarin-6 loaded liposomes. The particle size of the PEG or TPGS coated liposomes was ranged between 126 and 191nm. High-resolution field-emission transmission electron microscopy (FETEM) confirmed the coating of TPGS on the liposomes. The IC50 value, which is the drug concentration needed to kill 50% cells in a designated time period, was found to be 37.04±1.05, 31.04±0.75, 7.70±0.22, and 5.93±0.57?g/ml for the commercial Taxotere(®), the nude, PEG coated and TPGS coated liposomes, respectively after 24h culture with C6 glioma cells. The TPGS coated liposomes showed great advantages in vitro than the PEG coated liposomes. PMID:22001537
Effects of chitosan coating on physical properties and pharmacokinetic behavior of mitoxantrone liposomes.
Zhuang, Jie; Ping, Qineng; Song, Yunmei; Qi, Jianping; Cui, Zheng
The objective of this work was to evaluate the physical properties and in vivo circulation of chitosan (CH)-coated liposomes of mitoxantrone (MTO). Changes in particle size and zeta potential confirmed the existence of a coating layer on the surface of liposomes. The in vitro release of adsorbed CH from the liposomes was significantly slower than CH solution, indicating the stable interaction between CH and liposomes. The physical stability of the CH-coated liposomes was evaluated by measuring the change in particle size before and after freeze-drying and rehydration. The smallest change was observed when saturated adsorption of CH occurred (0.3%). The sustained release in vitro of MTO from CH-coated liposomes confirmed the increased stability of liposomes. Systemic circulation of CH-coated MTO liposomes was examined. The 0.3% CH-coated liposomes showed the longest circulation time. It could be concluded that the prolonged retention time of the liposomes was closely related with CH coating and its stability effect. PMID:20957162
Pre-Targeting and Direct Immunotargeting of Liposomal Drug Carriers to Ovarian Carcinoma
Lehtinen, Julia; Raki, Mari; Bergström, Kim A.; Uutela, Päivi; Lehtinen, Katariina; Hiltunen, Annukka; Pikkarainen, Jere; Liang, Huamin; Pitkänen, Sari; Määttä, Ann-Marie; Ketola, Raimo A.; Yliperttula, Marjo; Wirth, Thomas; Urtti, Arto
Background Epidermal growth factor receptor (EGFR) is overexpressed in many solid tumor types, such as ovarian carcinoma. Immunoliposome based drug targeting has shown promising results in drug delivery to the tumors. However, the ratio of tumor-to-normal tissue concentrations should be increased to minimize the adverse effects of cytostatic drugs. Methodology/Principal Findings We studied the EGFR-targeted doxorubicin immunoliposomes using pre-targeting and local intraperitoneal (i.p.) administration of the liposomes. This approach was used to increase drug delivery to tumors as compared to direct intravenous (i.v.) administration of liposomes. EGFR antibodies were attached on the surface of PEG coated liposomes using biotin-neutravidin binding. Receptor mediated cellular uptake and cytotoxic efficacy of EGFR-targeted liposomes were investigated in human ovarian adenocarcinoma (SKOV-3 and SKOV3.ip1) cells. In vivo distribution of the liposomes in mice was explored using direct and pre-targeting approaches and SPECT/CT imaging. Targeted liposomes showed efficient and specific receptor-mediated binding to ovarian carcinoma cells in vitro, but the difference in cytotoxicity between targeted and non-targeted liposomes remained small. The relatively low cytotoxic efficacy is probably due to insufficient doxorubicin release from the liposomes rather than lack of target binding. Tumor uptake of targeted liposomes in vivo was comparable to that of non-targeted liposomes after both direct and pre-targeting administration. For both EGFR-targeted and non-targeted liposomes, the i.p. administration increased liposome accumulation to the tumors compared to i.v. injections. Conclusions/Significance Intraperitoneal administration of liposomes may be a beneficial approach to treat the tumors in the abdominal cavity. The i.p. pre-targeting method warrants further studies as a potential approach in cancer therapy. PMID:22844475
Negatively charged liposomes show potent adjuvant activity when simply admixed with protein antigens
Yanasarn, Nijaporn; Sloat, Brian R.; Cui, Zhengrong
Liposomes have been investigated extensively as a vaccine delivery system. Herein the adjuvant activities of liposomes with different net surface charges (neutral, positive, or negative) were evaluated when admixed with protein antigens, ovalbumin (OVA, pI = 4.7), Bacillus anthracis protective antigen protein (PA, pI = 5.6), or cationized OVA (cOVA). Mice immunized subcutaneously with OVA admixed with different liposomes generated different antibody responses. Interestingly, OVA admixed with net negatively charged liposomes prepared with DOPA was as immunogenic as OVA admixed with positively charged liposomes prepared with DOTAP. Immunization of mice with the anthrax PA protein admixed with the net negatively charged DOPA liposomes also induced a strong and functional anti-PA antibody response. When the cationized OVA was used as a model antigen, liposomes with net neutral, negative, or positive charges showed comparable adjuvant activities. Immunization of mice with the OVA admixed with DOPA liposomes also induced OVA-specific CD8+ cytotoxic T lymphocyte responses and significantly delayed the growth of OVA-expressing B16-OVA tumors in mice. However, not all net negatively charged liposomes showed a strong adjuvant activity. The adjuvant activity of the negatively charged liposomes may be related to the liposome's ability (i) to up-regulate the expression of molecules related to the activation and maturation of antigen-presenting cells and (ii) to slightly facilitate the uptake of the antigens by antigen-presenting cells. Simply admixing certain negatively charged liposomes with certain protein antigens of interest may represent a novel platform for vaccine development. PMID:21615153
Resuscitation Using Liposomal Vasopressin in an Animal Model of Uncontrolled Hemorrhagic Shock
Ho, Ja-An Annie; Fan, Nien-Chu; Yang, Ya-Lin; Lee, Chien-Chang; Chen, Shyr-Chyr
Background Current research suggests that administration of vasopressin to patients with uncontrolled hemorrhagic shock (UHS) can avoid the detrimental effects associated with aggressive fluid resuscitation. However, vasopressin has a short half-life of 10~35 minutes in in vivo use and precludes its use in the pre-hospital setting. To increase the half-life of vasopressin, we proposed to synthesize liposome-encapsulated vasopressin and test it in a rat model of UHS. Methods The film hydration method was used to prepare liposomal vasopressin consisting of: Dipalmitoylphosphatidylcholine, cholesterol, and dipalmitoyl phosphatidylethanolamine (20:20:1 mole ratio). 42 rats were subjected to UHS and randomly received 5 different treatments (vasopressin, liposomal vasopressin, lactate ringer (LR), liposome only and sham). Outcome of UHS were measured using 4 common prognostic tests: mean arterial pressure (MAP), serum lactate level, inflammatory profile and pulmonary edema. Results The dynamic light scattering results confirmed that we had prepared a successful liposomal vasopressin complex. Comparing the serum vasopressin concentration of liposomal vasopressin and vasopressin treated animals by ELISA, we found that the concentration of vasopressin for the liposomal vasopressin treated group is higher at 60 minutes. However, there was no significant difference between the MAP profile of rats treated with vasopressin and liposomal vasopressin in UHS. We also observed that animals treated with liposomal vasopressin performed indifferently to vasopressin treated rats in serum lactate level, inflammatory profile and edema profile. For most of our assays, the liposome only control behaves similarly to LR resuscitation in UHS rats. Conclusion We have synthesized a liposomal vasopressin complex that can prolong the serum concentration of vasopressin in a rat model of UHS. Although UHS rats treated with either liposomal vasopressin or vasopressin showed no statistical differences, it would be worthwhile to repeat the experiments with different liposomal compositions. PMID:26154286
Transient cerebral hypoperfusion assisted intraarterial cationic liposome delivery to brain tissue
Joshi, Shailendra; Singh-Moon, Rajinder P.; Wang, Mei; Chaudhuri, Durba B.; Holcomb, Mark; Straubinger, Ninfa L.; Bruce, Jeffrey N.; Bigio, Irving J.; Straubinger, Robert M.
Object Transient cerebral hypoperfusion (TCH) has empirically been used to assist intraarterial (IA) drug delivery to brain tumors. Transient (< 3 min) reduction of cerebral blood flow (CBF) occurs during many neuro- and cardiovascular interventions and has recently been used to better target IA drugs to brain tumors. In the present experiments, we assessed whether the effectiveness of IA delivery of cationic liposomes could be improved by TCH. Methods Cationic liposomes composed of 1:1 DOTAP:PC (dioleoyl-trimethylammonium-propane:phosphatidylcholine) were administered to three groups of Sprague Dawley rats. In the first group, we tested the effect of blood flow reduction on IA delivery of cationic liposomes. In the second group, we compared TCH-assisted IA liposomal delivery vs. intravenous (IV) administration of the same dose. In the third group, we assessed retention of cationic liposomes in brain four hours after TCH assisted delivery. The liposomes contained a near infrared dye, DilC18(7), whose concentration could be measured in vivo by diffuse reflectance spectroscopy. Results IA injections of cationic liposomes during TCH increased their delivery approximately four-fold compared to injections during normal blood flow. Optical pharmacokinetic measurements revealed that relative to IV injections, IA injection of cationic liposomes during TCH produced tissue concentrations that were 100-fold greater. The cationic liposomes were retained in the brain tissue four hours after a single IA injection. There was no gross impairment of neurological functions in surviving animals. Conclusions Transient reduction in CBF significantly increased IA delivery of cationic liposomes in the brain. High concentrations of liposomes could be delivered to brain tissue after IA injections with concurrent TCH while none could be detected after IV injection. IA-TCH injections were well tolerated and cationic liposomes were retained for at least 4 hours after IA administration. These results should encourage development of cationic liposomal formulations of chemotherapeutic drugs and their IA delivery during TCH. PMID:24664370
Effect of liposomes on the absorption of water-soluble active pharmaceutical ingredients via oral administration.
Yang, Zhijun; Lu, Aiping; Wong, Blenda Chi Kwan; Chen, Xiaoyu; Bian, Zhaoxiang; Zhao, Zhongzhen; Huang, Wenhua; Zhang, Ge; Chen, Hubiao; Xu, Min
The objective of this study was to investigate the effect of liposomes on the absorption of water-soluble active pharmaceutical ingredients. Salbutamol sulfate (SBS) has been widely used for treatment of bronchospasm in conditions such as asthma. Using SBS as the model drug in this study, we developed SBS-loaded liposomes for oral administration and explored the relationship between their bioavailability and anti-asthmatic efficacy. SBS was entrapped in liposomes with encapsulation efficiency as high as 70%. The in vitro transport profile of SBS across a dialysis membrane for liposome suspension was compared with that for free SBS solution. Oral administration of liposomes labeled with the fluorescent dye 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide (DiR) in a mouse model was assessed by a small animal imaging system. Pharmacokinetic and pharmacodynamic studies on SBS liposome suspension and free SBS solution were performed using animal models via oral administration. The results showed that liposomes could sustain the release of SBS in vitro and decrease the transport rate of SBS across the dialysis membrane. In vivo fluorescence imaging analysis demonstrated DiR liposome distribution in mouse stomach for at least 24 hr. The mean residence time of SBS from liposomes was found to be longer than that of free SBS, suggesting that the relative bioavailability of SBS was higher when liposome delivery was used. The pharmacokinetic data also showed that the drug absorption rate was relatively slower for treatment with liposomal SBS when compared to free SBS. Moreover, SBS liposome suspension was shown to give a prolonged anti-asthmatic effect after oral administration when compared to free SBS solution. Overall, this study demonstrated that use of liposomes as delivery vehicles for sustained drug release and controlled absorption could be a promising approach for improving the therapeutic potency of active pharmaceutical ingredients. PMID:23621538
Liposome-encapsulated peptides protect against experimental allergic encephalitis
Belogurov, Alexey A.; Stepanov, Alexey V.; Smirnov, Ivan V.; Melamed, Dobroslav; Bacon, Andrew; Mamedov, Azad E.; Boitsov, Vitali M.; Sashchenko, Lidia P.; Ponomarenko, Natalia A.; Sharanova, Svetlana N.; Boyko, Alexey N.; Dubina, Michael V.; Friboulet, Alain; Genkin, Dmitry D.; Gabibov, Alexander G.
Multiple sclerosis (MS) is a severe inflammatory and neurodegenerative disease with an autoimmune background. Despite the variety of therapeutics available against MS, the development of novel approaches to its treatment is of high importance in modern pharmaceutics. In this study, experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats has been treated with immunodominant peptides of the myelin basic protein (MBP) encapsulated in mannosylated small unilamellar vesicles. The results show that liposome-encapsulated MBP46–62 is the most effective in reducing maximal disease score during the first attack, while MBP124–139 and MBP147–170 can completely prevent the development of the exacerbation stage. Both mannosylation of liposomes and encapsulation of peptides are critical for the therapeutic effect, since neither naked peptides nor nonmannosylated liposomes, loaded or empty, have proved effective. The liposome-mediated synergistic effect of the mixture of 3 MBP peptides significantly suppresses the progression of protracted EAE, with the median cumulative disease score being reduced from 22 to 14 points, compared to the placebo group; prevents the production of circulating autoantibodies; down-regulates the synthesis of Th1 cytokines; and induces the production of brain-derived neurotrophic factor in the central nervous system. Thus, the proposed formulation ameliorates EAE, providing for a less severe first attack and rapid recovery from exacerbation, and offers a promising therapeutic modality in MS treatment.—Belogurov, A. A., Jr., Stepanov, A. V., Smirnov, I. V., Melamed, D., Bacon, A., Mamedov, A. E., Boitsov, V. M., Sashchenko, L. P., Ponomarenko, N. A., Sharanova, S. N., Boyko, A. N., Dubina, M. V., Friboulet, A., Genkin, D. D., Gabibov, A. G. Liposome-encapsulated peptides protect against experimental allergic encephalitis. PMID:23047895
Supramolecular tetrad featuring covalently linked bis(porphyrin)-phthalocyanine coordinated to fullerene: construction and photochemical studies.
K C, Chandra B; Lim, Gary N; Karr, Paul A; D'Souza, Francis
A multimodular donor-acceptor tetrad featuring a bis(zinc porphyrin)-(zinc phthalocyanine) ((ZnP-ZnP)-ZnPc) triad and bis-pyridine-functionalized fullerene was assembled by a "two-point" binding strategy, and investigated as a charge-separating photosynthetic antenna-reaction center mimic. The spectral and computational studies suggested that the mode of binding of the bis-pyridine-functionalized fullerene involves either one of the zinc porphyrin and zinc phthalocyanine (Pc) entities of the triad or both zinc porphyrin entities leaving ZnPc unbound. The binding constant evaluated by constructing a Benesi-Hildebrand plot by using the optical data was found to be 1.17×10(5) M(-1), whereas a plot of "mole-ratio" method revealed a 1:1 stoichiometry for the supramolecular tetrad. The mode of binding was further supported by differential pulse voltammetry studies, in which redox modulation of both zinc porphyrin and zinc phthalocyanine entities was observed. The geometry of the tetrad was deduced by B3LYP/6-31G* optimization, whereas the energy levels for different photochemical events was established by using data from the optical absorption and emission, and electrochemical studies. Excitation of the zinc porphyrin entity of the triad and tetrad revealed ultrafast singlet-singlet energy transfer to the appended zinc phthalocyanine. The estimated rate of energy transfer (k(ENT)) in the case of the triad was found to be 7.5×10(11) s(-1) in toluene and 6.3×10(11) s(-1) in o-dichlorobenzene, respectively. As was predicted from the energy levels, photoinduced electron transfer from the energy-transfer product, that is, singlet-excited zinc phthalocyanine to fullerene was verified from the femtosecond-transient spectral studies, both in o-dichlorobenzene and toluene. Transient bands corresponding to ZnPc(?+) in the 850?nm range and C60(?-) in the 1020?nm range were clearly observed. The rate of charge separation, k(CS), and rate of charge recombination, k(CR), for the (ZnP-ZnP)-ZnPc(?+):Py2C60(?-) radical ion pair (from the time profile of 849?nm peak) were found to be 2.20×10(11) and 6.10×10(8) s(-1) in toluene, and 6.82×10(11) and 1.20×10(9) s(-1) in o-dichlorobenzene, respectively. These results revealed efficient energy transfer followed by charge separation in the newly assembled supramolecular tetrad. PMID:24805781
Computer-aided design of liposomal drugs: In silico prediction and experimental validation of drug candidates for liposomal remote loading.
Cern, Ahuva; Barenholz, Yechezkel; Tropsha, Alexander; Goldblum, Amiram
Previously we have developed and statistically validated Quantitative Structure Property Relationship (QSPR) models that correlate drugs' structural, physical and chemical properties as well as experimental conditions with the relative efficiency of remote loading of drugs into liposomes (Cern et al., J. Control. Release 160 (2012) 147-157). Herein, these models have been used to virtually screen a large drug database to identify novel candidate molecules for liposomal drug delivery. Computational hits were considered for experimental validation based on their predicted remote loading efficiency as well as additional considerations such as availability, recommended dose and relevance to the disease. Three compounds were selected for experimental testing which were confirmed to be correctly classified by our previously reported QSPR models developed with Iterative Stochastic Elimination (ISE) and k-Nearest Neighbors (kNN) approaches. In addition, 10 new molecules with known liposome remote loading efficiency that were not used by us in QSPR model development were identified in the published literature and employed as an additional model validation set. The external accuracy of the models was found to be as high as 82% or 92%, depending on the model. This study presents the first successful application of QSPR models for the computer-model-driven design of liposomal drugs. PMID:24184343
Cryogenic transmission electron microscopy of recombinant tuberculosis vaccine antigen with anionic liposomes reveals formation of flattened liposomes
Fox, Christopher B; Mulligan, Sean K; Sung, Joyce; Dowling, Quinton M; Fung, H W Millie; Vedvick, Thomas S; Coler, Rhea N
Development of lipid-based adjuvant formulations to enhance the immunogenicity of recombinant vaccine antigens is a focus of modern vaccine research. Characterizing interactions between vaccine antigens and formulation excipients is important for establishing compatibility between the different components and optimizing vaccine stability and potency. Cryogenic transmission electron microscopy (TEM) is a highly informative analytical technique that may elucidate various aspects of protein- and lipid-based structures, including morphology, size, shape, and phase structure, while avoiding artifacts associated with staining-based TEM. In this work, cryogenic TEM is employed to characterize a recombinant tuberculosis vaccine antigen, an anionic liposome formulation, and antigen–liposome interactions. By performing three-dimensional tomographic reconstruction analysis, the formation of a population of protein-containing flattened liposomes, not present in the control samples, was detected. It is shown that cryogenic TEM provides unique information regarding antigen–liposome interactions not detectable by light-scattering-based methods. Employing a suite of complementary analytical techniques is important to fully characterize interactions between vaccine components. PMID:24648734
Computer-aided design of liposomal drugs: in silico prediction and experimental validation of drug candidates for liposomal remote loading
Cern, Ahuva; Barenholz, Yechezkel; Tropsha, Alexander; Goldblum, Amiram
Previously we have developed and statistically validated Quantitative Structure Property Relationship (QSPR) models that correlate drugs' structural, physical and chemical properties as well as experimental conditions with the relative efficiency of remote loading of drugs into liposomes (Cern et al, Journal of Controlled Release, 160(2012) 14–157). Herein, these models have been used to virtually screen a large drug database to identify novel candidate molecules for liposomal drug delivery. Computational hits were considered for experimental validation based on their predicted remote loading efficiency as well as additional considerations such as availability, recommended dose and relevance to the disease. Three compounds were selected for experimental testing which were confirmed to be correctly classified by our previously reported QSPR models developed with Iterative Stochastic Elimination (ISE) and k-nearest neighbors (kNN) approaches. In addition, 10 new molecules with known liposome remote loading efficiency that were not used in QSPR model development were identified in the published literature and employed as an additional model validation set. The external accuracy of the models was found to be as high as 82% or 92%, depending on the model. This study presents the first successful application of QSPR models for the computer-model-driven design of liposomal drugs. PMID:24184343
The PEGylated liposomal doxorubicin improves the delivery and therapeutic efficiency of 188Re-Liposome by modulating phagocytosis in C26 murine colon carcinoma tumor model.
Hsu, Wei-Hsin; Liu, Si-Yen; Chang, Ya-Jen; Chang, Chih-Hsien; Ting, Gann; Lee, Te-Wei
Liposome in delivering radionuclide for cancer therapy has been expansively studied; however, liposome itself can be deliberately entrapped and destroyed by the reticuloendothelial system, causing an insufficiency of the drug delivery, which in turn would restrict the effectiveness of the drug. In this study, mice with subcutaneous implantation of C26 murine colon cancer received an experimental treatment regimen in which mice took delivery of PEGylated liposomal doxorubicin (LipoDox) first, after a three-day interval, of Rhenium-188 encapsulated into PEGylated liposome ((188)Re-Liposome) subsequently and by which suppressed the functioning of reticuloendothelial system for the short term. The data showed that based upon the biodistribution assay and the evaluation of the therapeutic efficacy, (188)Re-Liposome was more sufficiently delivered to tumor sites in mice with this treatment regimen than mice without the regimen, and that cancer mortalities in mice with the treatment regimen were much lower than the mortalities in mice without the regimen. Taken together, a new strategy proposed in this study significantly improved both the (188)Re-Liposome delivery and the effectiveness of (188)Re-Liposome, suggesting that the strategy can be an ideal treatment for cancer. PMID:25027866
Infrared spectra of phthalocyanine and naphthalocyanine in sandwich-type (na)phthalocyaninato and porphyrinato rare earth complexes. Part 3. The effects of substituents and molecular symmetry on the infrared characteristics of phthalocyanine in bis(phthalocyaninato) rare earth complexes
Fanli Lu; Meng Bao; Changqin Ma; Xianxi Zhang; Dennis P. Arnold; Jianzhuang Jiang
The infra-red (IR) spectroscopic data for a series of 45 homoleptic unsubstituted and substituted bis(phthalocyaninato) rare earth complexes M(Pc)2 and M(Pc*)2 [M=Y, La…Lu except Pm; H2Pc=phthalocyanine; H2Pc*=2,3,9,10,16,17,24,25-octakis(octyloxy)phthalocyanine (H2OOPc) and 2(3),9(10),16(17),24(25)-tetra(tert-butyl)phthalocyanine (H2TBPc)] have been collected with resolution of 2 cm?1. The IR spectra for M(Pc)2 and M(OOPc)2 are much simpler than those of M(TBPc)2, revealing the relatively higher symmetry of the
Processing of different liposome markers after in vitro uptake of immunoglobulin-coated liposomes by rat liver macrophages.
Derksen, J T; Morselt, H W; Scherphof, G L
We compared the metabolic fate of [3H]cholesteryl[14C]oleate, [3H]cholesteryl hexadecylether, 125I-labeled bovine serum albumin and [3H]inulin as constituents of large immunoglobulin-coupled unilamellar lipid vesicles following their internalization by rat liver macrophages (Kupffer cells) in monolayer culture. Under serum-free conditions, the cholesteryl oleate that is taken up is hydrolyzed, for the greater part, within 2 h. This occurs in the lysosomal compartment as judged by the inhibitory effect of the lysosomotropic agents monensin and chloroquin. After hydrolysis, the cholesterol moiety is accommodated in the cellular pool of free cholesterol and the oleate is reutilized for the synthesis mainly of phospholipids and, to a lesser extent of triacylglycerols. During incubation in plasma, however, substantial proportions of both the cholesterol and the oleate are shed from the cells, predominantly in the unesterified form. When the liposomes are labeled with the cholesteryl ester analog [3H]cholesteryl hexadecylether only a very small fraction of the label is released from the cells, even in the presence of plasma. Similar to the label remaining associated with the cells, the released label is identified in that case as unchanged cholesteryl ether. The liposomal aqueous phase marker 125I-labeled bovine serum albumin is also readily degraded intralysosomally and the radioactive label is rapidly released from the cells in a trichloroacetic acid-soluble form. Also, as much as 20% of the aqueous phase marker [3H]inulin that becomes cell-associated during a 2-h incubation with inulin-containing liposomes, is released from the cells during a subsequent 4-h incubation period in medium or rat plasma. The usefulness of the various liposomal labels as parameters of liposome uptake and intracellular processing is discussed. PMID:3651512
Curcuminoids-loaded liposomes in combination with arteether protects against Plasmodium berghei infection in mice.
Aditya, N P; Chimote, Geetanjali; Gunalan, Karthigayan; Banerjee, Rinti; Patankar, Swati; Madhusudhan, Basavaraj
Curcuminoids are poorly water-soluble compounds with promising antimalarial activity. To overcome some of the drawbacks of curcuminoids, we explored the potential of liposomes for the intravenous delivery of curcuminoids in a model of mouse malaria. The curcuminoids-loaded liposomes were formulated from phosphatidylcholine (soy PC) by the thin-film hydration method. Antimalarial activity of curcuminoids-loaded liposomes alone and in combination with ?/? arteether when administered intravenously, was evaluated in Plasmodium berghei infected mice. Animals treated with curcuminoids-loaded liposomes showed lower parasitemia and higher survival when compared to control group (no treatment). Importantly, the combination therapy of curcuminoids-loaded liposomes (40 mg/kg body wt) along with ?/? arteether (30 mg/kg body wt) was able to not only cure infected mice but also prevented recrudescence. These data suggest that curcuminoids-loaded liposomes may show promise as a formulation for anti-malarial therapy. PMID:22561991
Liposomes Assembled from a Dual Drug-tailed Phospholipid for Cancer Therapy.
Fang, Shuo; Niu, Yuge; Zhu, Wenjun; Zhang, Yemin; Yu, Liangli; Li, Xinsong
We report a novel dual drug-tailed phospholipid which can form liposomes as a combination of prodrug and drug carrier. An amphiphilic dual chlorambucil-tailed phospholipid (DCTP) was synthesized by a straightforward esterification. With two chlorambucil molecules as hydrophobic tails and one glycerophosphatidylcholine molecule as a hydrophilic head, the DCTP, a phospholipid prodrug, undergoes assembly to form a liposome without any additives by the thin lipid film technique. The DCTP liposomes, as an effective carrier of chlorambucil, exhibited a very high loading capacity and excellent stability. The liposomes had higher cytotoxic effects to cancer cell lines than free DCTP and chlorambucil. The in vivo antitumor activity assessment indicated that the DCTP liposomes could inhibit the tumor growth effectively. This novel strategy of dual drug-tailed phospholipid liposomes may be also applicable to other hydrophobic anticancer drugs which have great potential in cancer therapy. PMID:25690917
Reduced dose-limiting toxicity of intraperitoneal mitoxantrone chemotherapy using cardiolipin-based anionic liposomes.
Chang, Rae Sung; Kim, Jiyeon; Lee, Han Young; Han, Su-Eun; Na, Jinhee; Kim, Kwangmeyung; Kwon, Ick Chan; Kim, Young Bong; Oh, Yu-Kyoung
Intraperitoneal chemotherapy confers limited clinical benefit as a result of the dose-limiting toxicity of anticancer drugs. We aimed to develop optimized liposomes for mitoxantrone (MTO) administration that provide high encapsulation efficiency and increase the therapeutic index. Cationic MTO was loaded onto anionic liposomes by electrostatic surface complexation. The anticancer activity was evaluated in a peritoneal carcinomatosis model. The retention of MTO at the tumor site was monitored by molecular imaging. MTO loading efficiencies by electrostatic complexation were >95% for all anionic liposomes but <5% for neutral liposomes. Among anionic liposomes, cardiolipin liposomes (CLs) exhibited the strongest binding affinity for MTO, the highest anticancer activity, and the lowest toxicity. MTO delivered by CLs showed prolonged retention at tumor sites. Unlike free MTO showing significant cardiotoxicity, MTO administered in CLs provided negligible cardiotoxicity. CL-mediated delivery may increase the therapeutic index of MTO chemotherapy by prolonged retention and reduced cardiotoxicity. PMID:20570638
Spectroscopic investigation of different concentrations of the vapour deposited copper phthalocyanine as a "guest" in polyimide matrix.
Georgiev, Anton; Yordanov, Dancho; Dimov, Dean; Assa, Jacob; Spassova, Erinche; Danev, Gencho
Nanocomposite layers 250 nm copper phthalocyanine/polyimide prepared by simultaneous vapour deposition of three different sources were studied. Different concentrations of copper phthalocyanine as a "guest" in polyimide matrix as a function of conditions of the preparation have been determined by FTIR (Fourier Transform Infrared) and UV-VIS (Ultraviolet-Visible) spectroscopies. The aim was to estimate the possibility of the spectroscopic methods for quantitative determination of the "guest" and compare with the quality of the polyimide thin films in relation to the "guest" concentration. The band at 1334 cm(-1) has been used for quantitative estimation of "guest" in polyimide matrix. The concentrations of the copper phthalocyanine less than 20% require curve fitting techniques with Fourier self deconvolution. The relationship between "guest" concentrations and degree of imidization, as well as the electronic UV-VIS spectra are discussed in relation to the composition, imidization degree and the two crystallographic modification of the embedded chromophore. PMID:25638427
Ammonia adsorption on iron phthalocyanine on Au(111): Influence on adsorbate-substrate coupling and molecular spin
NASA Astrophysics Data System (ADS)
Isvoranu, Cristina; Wang, Bin; Ataman, Evren; Schulte, Karina; Knudsen, Jan; Andersen, Jesper N.; Bocquet, Marie-Laure; Schnadt, Joachim
The adsorption of ammonia on Au(111)-supported monolayers of iron phthalocyanine has been investigated by x-ray photoelectron spectroscopy, x-ray absorption spectroscopy, and density functional theory calculations. The ammonia-induced changes of the x-ray photoemission lines show that a dative bond is formed between ammonia and the iron center of the phthalocyanine molecules, and that the local spin on the iron atom is quenched. This is confirmed by density functional theory, which also shows that the bond between the iron center of the metalorganic complex and the Au(111) substrate is weakened upon adsorption of ammonia. The experimental results further show that additional adsorption sites exist for ammonia on the iron phthalocyanine monolayer.
Optical characterization and analysis of the gas\\/surface adsorption phenomena on phthalocyanines thin films for gas sensing application
J. Spadavecchia; G. Ciccarella; R. Rella
Zn(II) tetra-4-(2,4-di-t-amylphenoxy)-phthalocyanine (1a), Zn(II) tris-(2,4-di-t-amylphenoxy)-[4-(4-mercapto-phenylimino-methyl)-phenoxy] (1b) and Zn(II) tris-(2,4-di-t-amylphenoxy)-[4-(4-formyl)-phenoxy] (1c) phthalocyanine were synthesized. The molecular structures were confirmed by LC–MS, 1H NMR, FT-IR and UV–vis spectra. Spin coated layers of these phthalocyanines have been used as optochemically interactive materials for the detection of volatile organic compounds (VOCs) in the UV–vis spectral range. An optical characterization in controlled atmosphere have been
Hyperthermia and Thermosensitive Liposomes for Improved Delivery of Chemotherapeutic Drugs to Solid Tumors
Gerben A. Koning; Alexander M. M. Eggermont; Lars H. Lindner; Timo L. M. ten Hagen
Lipid-based nanocarriers or liposomes have been proven successful in the delivery of chemotherapeutic agents and are currently\\u000a applied clinically in the treatment of various types of cancer. Liposomes offer the advantage of a high drug payload, decreased\\u000a drug toxicity and enhanced drug accumulation at tumor sites. Increased accumulation is due to the relatively leaky tumor vasculature\\u000a that allows liposome extravasation.
Microcalorimetric studies of the effects of artesunate liposomes on the metabolism of Escherichia coli during growth
Shen XuesongWang; Wang Tao; Jin Meihua; Zhao Chunxia; Qin Xuelian; Liu Hanfu; Qiu Zhuangping; Liu Yi
A thermal dynamic model of nanoformulations entrapped in artesunate liposomes was established and biological thermodynamics\\u000a was applied for investigation of the drug formulations. Effects of artesunate liposomes on the growth metabolism of Escherichia coli were studied by microcalorimetry. The results showed that (1) Comparison of artesunate and artesunate liposomes, the thermogenesis\\u000a curves of E. coli were significant different in the
Negatively charged liposomes show potent adjuvant activity when simply admixed with protein antigens.
Yanasarn, Nijaporn; Sloat, Brian R; Cui, Zhengrong
Liposomes have been investigated extensively as a vaccine delivery system. Herein the adjuvant activities of liposomes with different net surface charges (neutral, positive, or negative) were evaluated when admixed with protein antigens, ovalbumin (OVA, pI = 4.7), Bacillus anthracis protective antigen protein (PA, pI = 5.6), or cationized OVA (cOVA). Mice immunized subcutaneously with OVA admixed with different liposomes generated different antibody responses. Interestingly, OVA admixed with net negatively charged liposomes prepared with DOPA was as immunogenic as OVA admixed with positively charged liposomes prepared with DOTAP. Immunization of mice with the anthrax PA protein admixed with the net negatively charged DOPA liposomes also induced a strong and functional anti-PA antibody response. When the cationized OVA was used as a model antigen, liposomes with net neutral, negative, or positive charges showed comparable adjuvant activities. Immunization of mice with the OVA admixed with DOPA liposomes also induced OVA-specific CD8(+) cytotoxic T lymphocyte responses and significantly delayed the growth of OVA-expressing B16-OVA tumors in mice. However, not all net negatively charged liposomes showed a strong adjuvant activity. The adjuvant activity of the negatively charged liposomes may be related to the liposome's ability (i) to upregulate the expression of molecules related to the activation and maturation of antigen-presenting cells and (ii) to slightly facilitate the uptake of the antigens by antigen-presenting cells. Simply admixing certain negatively charged liposomes with certain protein antigens of interest may represent a novel platform for vaccine development. PMID:21615153
Viability of mammalian embryos subjected to liposome interaction or centrifugation for gene transfer
Loskutoff, Nadia Mikhail
and pregnancy rate Glycerol and chloroquine effects . Liposome injections Combination glycerol and chloroquine effects Calcein-entrapped liposome injections Centrifugation effects . DISCUSSION AND SUMMARY 5 8 15 18 20 24 29 31 34 37 39 45 45... combination treatment of chloroquine plus glycerol (v/v medium). 5b: Angular transformation of data listed in Table 5a 51 6a: Embryo fluorescence resulting from calcein-entrapped liposome injections into the perivitelline space followed by glycerol...
Novel irinotecan-loaded liposome using phytic acid with high therapeutic efficacy for colon tumors
Yoshiyuki Hattori; Li Shi; Wuxiao Ding; Kimiko Koga; Kumi Kawano; Motoki Hakoshima; Yoshie Maitani
Phytic acid (IP-6) is a polyphosphorylated carbohydrate with antitumor activity for many kinds of tumors. In this study, we developed a novel method of loading irinotecan (CPT-11) into liposomes using IP-6, and evaluated its antitumor effect on colon tumors in vivo. Liposomal CPT-11 was prepared by loading CPT-11 to distearoylphosphatidylcholine\\/cholesterol\\/methoxy-poly(ethyleneglycol)-distearylphosphatidylethanolamine liposomes prepared in IP-6 solution, CuSO4 solution and citrate buffer,
Liposomes prolong the therapeutic effect of anti-asthmatic medication via pulmonary delivery
Chen, Xiaoyu; Huang, Wenhua; Wong, Blenda Chi; Yin, Linlin; Wong, Yuen Fan; Xu, Min; Yang, Zhijun
Purpose The main objective of this study was to develop a novel aerosolized liposome formulation for pulmonary delivery of anti-asthmatic medication and to explore the relationship between the bioavailability and anti-asthmatic efficacy of such a formulation. Asthma treatment usually requires frequent administration of medication for sustained bronchodilating response. Liposomes are known for their capability for sustained drug release and thus would be a suitable delivery system for anti-asthmatic medication for prolonged therapeutic effect. Salbutamol sulfate (SBS) was chosen as the model drug in this study because of its high water solubility and fast absorption after administration. Methods SBS was efficiently encapsulated into liposomes by the vesicular phospholipid gel technique. SBS permeability across the pulmonary membrane of an Asian toad was determined by in vitro study. Intratracheal administration of liposomes labeled with the fluorescent dye 1,1?-dioctadecyltetramethyl indotricarbocyanine iodide (DiR) in a rat model was assessed by a small animal imaging system and pharmacokinetic analysis. Pharmacodynamic analysis was performed in guinea pigs using the Konzett–Rössler method. Results SBS was efficiently encapsulated into liposomes with encapsulation efficiency as high as 70%. The particle size of the SBS liposome suspension was approximately 57 ± 21 nm. In the in vitro study of permeability across the pulmonary membrane of Asian toads, SBS from liposomes demonstrated a slower transport rate compared to free SBS solution. Pulmonary delivery of liposomes in a rat model showed that the liposomes were effectively distributed in the respiratory tract and lungs, and that the release of SBS from liposomes was sustained for at least 48 hours. Pharmacodynamic analysis in a guinea pig model showed that the anti-asthmatic effect of SBS liposomes persisted for up to 18 hours, whereas that of free SBS solution was less than 8 hours. Conclusion The overall results demonstrated that liposomes could increase the concentration and retention time of SBS in the lungs and therefore prolong its therapeutic effect. PMID:22412300
Calcium-dependent binding of uteroglobin (PCB-BP\\/CCSP) to negatively charged phospholipid liposomes
Magnus Nord; Jan-Ĺke Gustafsson; Johan Lund
To investigate interactions between the polychlorinated biphenyl-binding protein uteroglobin and phospholipids, we used a liposome-pelletting assay. PCB-BP\\/uteroglobin bound to liposomes made from negatively charged phospholipids (PtdSer and PtdIns) in the presence of 5 mM calcium. No binding to liposomes made from phospholipids without net charge (PtdChol and PtdEtn) was observed, nor could we detect binding in the absence of calcium
Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro
Robert J Lee; Philip S Low
Receptors for the vitamin folic acid are frequently overexpressed on epithelial cancer cells. To examine whether this overexpression might be exploited to specifically deliver liposome-encapsulated drug molecules in vitro, folate-targeted liposomes were prepared by incorporating 0.1 mol% of a folate-polyethyleneglycol-distearoylphosphatidylethanolamine (folate-PEG-DSPE) construct into the lipid bilayer, and were loaded with doxorubicin (DOX), an anti-cancer drug. Uptake of folate-PEG-liposomal DOX by
Liposome uptake into human colon adenocarcinoma cells in monlayer, spinner, and trypsinized cultures
Tom, B.H.; Macek, C.M.; Raphael, L.; Sengupta, J.; Cerny, E.A.; Jonah, M.M.; Rahman, Y.E.
The nature of liposome interactions with colon tumor cells was investigated. Thus, experiments were performed to study the uptake and incorporation of multilamellar and of reverse-phase evaporation liposomes of neutral charge into monolayers, suspended spinner cultures, and trypsinized cells of a human colon adenocarcinoma cell line, LS174T. The results showed that the same tumor cells cultured under each condition exhibited a distinct pattern of vesicle uptake as determined at 0, 15, 30, 60, and 120 min. In monolayer cultures of LS174T cells, the uptake of liposomes bearing (/sup 3/H)actinomycin D in the lipid bilayers was linear throughout the incubation period. In contrast, in trypsinized and spinner suspension cultures, uptake of liposomes was biphasic. There was a proportional uptake of both liposome (labeled with (/sup 3/H)phosphantidylcholine or (/sup 14/C)cholesterol) and of actinomycin D (trace labeled with /sup 3/H) into the cells under all culture conditions, indicating quantitative delivery of the drug with the intact lipid vesicle. Although the amount of actinomycin D presented to tumor cells by the two liposomes was equivalent, reverse-phase evaporation liposomes were more effectve than multilamellar vesicles in inhibiting uridine uptake. In the presence of excess liposomes (10 times the uptake studies), saturation of the tumor cell surface occurred by 120 min. However, the liposomes remained accessible to enzymatic removal for 60 min. Liposome-saturated tumor cells remained refractory to further binding of liposomes for at least 2 hr. The results thus revealed that differences in cell uptake were due to the state of the target cells and not the liposome types, or their differential leakage of labels.
The role of dioleoyl phosphatidylethanolamine in cationic liposome mediated gene transfer
Hassan Farhood; Natalya Serbina; Leaf Huang
In a reporter gene assay, cationic liposomes containing the cationic lipid 3?-(N-(N?,N?-dimethylaminoethane)carbamoyl)cholesterol (DC-Chol) and a neutral phospholipid dioleoylphosphatidylethanolamine (DOPE) showed high transfection activity. DNA\\/liposome complex which contained low amount of liposomes could bind to the cell surface but failed to transfect the cells. We have designed a two-step protocol to examine this phenomenon in more detail. A431 human cells were
An in vitro assay based on surface plasmon resonance to predict the in vivo circulation kinetics of liposomes.
Crielaard, B J; Yousefi, A; Schillemans, J P; Vermehren, C; Buyens, K; Braeckmans, K; Lammers, T; Storm, G
The adsorption of blood proteins onto liposomes and other colloidal particles is an important process influencing the circulation time. Proteins adsorbed to the surface of liposomes can mediate recognition of the liposomes by macrophages of the reticuloendothelial system (RES) facilitating their clearance from the circulation. Coating liposomes with poly(ethylene glycol) (PEG) decreases the blood clearance considerably, most likely due to reduced protein adsorption and/or liposome aggregation. By using the relation between clearance and protein binding, the present study introduces an in vitro assay measuring interactions of liposomes with proteins to predict their blood clearance in vivo. Such assay is valuable since it limits time and costs, and importantly reduces the number of animals required for pharmacokinetic investigations of new formulations. In the current study, Surface Plasmon Resonance (SPR) and fluorescence Single Particle Tracking (fSPT) were used to study liposome-protein interactions and blood induced liposome aggregation in vitro. By means of SPR the interactions between proteins and liposomes coated with PEG of different molecular weights and at different densities (PEG(2000) in 2.5%, 5% and 7%; PEG(5000) in 0.5%, 1.5% and 2.5%), were measured for several plasma proteins: human serum albumin (HSA), apolipoprotein E (ApoE), ?2-macroglobulin (?2-M), ?2-glycoprotein (?2-G) and fibronectin (Fn). Liposomes coated with PEG interacted less with all proteins, an effect which increased with the PEG surface density. In parallel, fSPT analysis showed that the exposure of liposomes to full blood did not change the liposome size, indicating that aggregation is not a strong attributive factor in the clearance of these liposomes. In addition, the SPR measurements of the interactions between liposomes and proteins were correlated with the blood clearance of the liposomes. For each protein, the degree of protein-liposome interaction as determined by SPR showed a moderate to strong positive correlation with the clearance of the liposome type. PMID:21803084
In vitro delivery of curcumin with cholesterol-based cationic liposomes.
Apiratikul, N; Penglong, T; Suksen, K; Svasti, S; Chairoungdua, A; Yingyongnarongkula, B
A new cholesterol-based cationic lipid was synthesized; liposomes prepared on its basis were evaluated as drug delivery vehicles for curcumin. Free and liposome-encapsulated curcumin cytotoxicity against HeLa, A549, HepG2, K562 and 1301 cell lines was assessed. Liposomal curcumin with ED50 values ranging from 2.5-10 microM exhibited 2-8 times higher cytotoxicity than free curcumin. The synthetic cholesterol-based cationic lipid also enhanced cellular uptake of curcumin into tested cells. Cationic liposome alone showed low cytotoxicity at high doses with ED50 values of 90-210 microM. PMID:24707732
Melittin liposomes surface modified with poloxamer 188: in vitro characterization and in vivo evaluation.
Tian, J L; Ke, X; Chen, Z; Wang, C J; Zhang, Y; Zhong, T C
Melittin liposomes surface modified with poloxamer 188 were developed, and the effect of poloxamer 188 was investigated with regard to anti-cancer effect and vascular stimulation. Melittin liposomes surface modified with poloxamer 188 at different concentrations (0%, 2%, and 5%) were prepared using the adsorption method, followed by in vitro characterization, including entrapment efficiency, zeta potential, particle size, and morphology. Subsequently, the influence of repeated freeze-thawing on the liposomes was investigated, and the effect of poloxamer 188 on the repeated freeze-thawing process was explored. Vascular stimulation effects of MLT, and MLT liposome that surface coated with or without poloxamer were all studied. Pharmacokinetics of the different MLT preparations were determined and the anticancer activity of the MLT formulations was investigated. The particle size of the liposomes gradually increased with increasing poloxamer 188 content, while the entrapment efficiency did not change significantly. After the first freeze-thaw cycle, size and PDI were both markedly reduced, entrapment efficiency rose, and there was no significant change of zeta potential. The vascular irritation caused by MLT could be reduced to an extent by encapsulation in liposome, but not completely eliminated, while liposomes coated with poloxamer 188 can effectively abolish the phenomenon. Melittin liposomes with surface modified by poloxamer exhibit enhanced bioavailability, effective anticancer activity, and reduced side effects compared with melittin solution. Poloxamer plays an important role in melittin liposomes. PMID:21699070
Antileishmanial and trypanocidal activities of new miltefosine liposomal formulations
A. Papagiannaros; C. Bories; C. Demetzos; P. M. Loiseau
Liposomes composed of hexadecylphosphocholine\\/egg phosphatidylcholine\\/stearylamine (HePC\\/EPC\\/SA) 10:10:0.1, 10:10:0.5 and 10:10:1 (molar ratio) (1–3) were prepared and lyophilized. The liposomes were physicochemically characterized (size and ?-potential) and they were found stable at 4 °C over a period of 4 weeks. In vitro, liposomes 1 and 2 were about twice more active than HePC against Leishmania donovani WT whereas liposomes 3 were about three