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Int J Curr Pharm Res, Vol 7, Issue 2, 21-28Review Article
1Research Scholar (M. Pharm.), Dr. L. H. Hiranandani College of Pharmacy, Ulhasnagar 421003, Maharashtra, India
Email: firstname.lastname@example.com
Received: 05 Mar 2015, Revised and Accepted: 30 Mar 2015
Objective: Chitosan is considerably versatile and promising biomaterial. It is a natural, tough, cationic, nontoxic, biodegradable, and biocompatible polymer obtained by alkaline deacetylation of chitin. Chitin is a polysaccharide obtained from exoskeletons of crustaceans and sea insects such as crab, krill, shrimp and crawfish etc. Besides the formerly mentioned resources it is also obtained from some fungi and bacterial cell walls.
Methods: Chitosan has found wide applicability in conventional pharmaceutical devices as a potential formulation excipient, some of which include binding, disintegrating, stabilizing, suspending, tablet coating, and film forming material. Chitosan has been comprehensively investigated for its suitability for its controlled release characteristics in various studies. Chitosan presents remarkable absorption and penetration enhancing properties that makes it a good candidate for the delivery of genes and peptide.
Results: It is possessing tremendous mucoadhesive and inherent anti-microbial properties, so that it can be used as a carrier for novel drug delivery. In addition to the above mentioned reasons, tailoring the controlled release and to improve the therapeutic efficacy of the low molecular weight drug compounds can also be achieved by this polymer and moreover in combination with various polymers is feasible due its compatibility i.e. low chemical reactivity.
Conclusion: This brief editorial epitomizes the potential application of chitosan in the development of drug delivery systems.
Keywords: Chitosan, Drug delivery, Gene delivery, Pharmaceutical applications.
Chitin, the second most abundant natural polysaccharide, is a straight homopolymer composed of β (1, 4)-linked GlcNAc (N-acetyl glucosamine) units with a three dimensional α-helical configuration stabilized by intramolecular hydrogen bonding [1]. Partial deacetylation of chitin results in the production of chitosan, which is a polysaccharide comprising copolymers of glucosamine and N-acetyl glucosamine.
Since chitosan exhibits favorable biological properties such as non-toxicity, biocompatibility, and biodegradability, it has attracted widespread interest in the pharmaceutical and biomedical fields [2, 3]. Along with these properties it also possesses some medical applications such as antimicrobial, hypocholesterolemic, antitumor, anti-inflammatory, antioxidant, angiotensin-I-converting enzyme (ACE) inhibition, excluding toxins from the intestines, reducing heavy-metal poisoning in humans, mucoadhesive, haemostatic, analgesic, radio-protective properties, preventing tooth decay and tooth diseases and immunity enhancing activities [4]. It is also widely used in biomedical industries for enzyme immobilization and purification, in chemical plants for wastewater treatment and in food industries for food formulations as binding, gelling, thickening and stabilizing agent [5].
The term chitosan is used to describe a series of chitosan polymers with different molecular weights (50 kDa to 2000 kDa), viscosity and degree of deacetylation [3]. The chemical structure of chitin and chitosan is shown in (fig. 1).
Fig. 1: Chemical structure of chitin and chitosan [6]
Application in drug delivery
Chitosan is widely used for nasal, vaginal, ophthalmic, transdermal & topical, buccal, parenteral, colon-specific and in implantable drug delivery etc. due to its favorable biological properties. Purity, the degree of acetylation, viscosity and molecular weight are the imperative factors of the chitosan ought to be taken in to consideration while selecting chitosan for the precise drug delivery. For the reason that, these qualities of this polymer decides the selection of an apt grade of chitosan as a material/carrier for a specific drug delivery [7].
This biodegradable polymer can be dissolved in mineral acid and organic acid aqueous solutions at particular conditions i.e. soluble in dilute acidic solutions below pH 6 [8-10]. The polyelectrolytic natures as well as chelating ability of the amine groups of the macromolecule determine the applications of chitosan. The amine groups of chitosan are protonated to NH3+in acidic solution, and accordingly chitosan's polyelectrolytic and chelating properties are essentially dominated by the acidity of the-NH3+[11]. It is used in the form of tablets, gels etc. (table 1).
Table 1: List of chitosan based formulations prepared by different methods [12]
|Types of systems
|Methods of preparation
|5-ASA, Diclofenac Sodium, Theophylline, Mesalamine, Glipizide.Propranolol HCl.
|Capsule shell
|Emulsion cross-linkingCoacervation/precipitationSpray-dryingIonic gelationSieving method
|Gentamicin Sulphate, Hemoglobin, Diclofenac, Clarithromicin.Propranolol-HCl.Cimetidine, Famotidine, Bovine serum albumin.Bovine serum albumin.Clozapine.
|Emulsion-droplet coalescenceCoacervation/precipitationIonic gelationReverse micellar method
|Gadopentetic acid.Bovine serum albumin, Ovalbumin.Ascorbic acid, Cyclosporine A.Doxorubicin.
|Bovine serum albumin, Insulin.
|Solution casting
|Ofloxacin, Paclitaxel.
Ophthalmic drug delivery system
The potential use of chitosan-based ophthalmic drug delivery systems is enhanced retention and biodistribution of drugs applied topically onto the eye. Chitosan is a suitable material for the design of ocular drug delivery systems mainly because it has admirable bio adhesion and penetration enhancing properties together with appropriate ocular tolerability and less or non-toxicity and allergenicity. Chitosan-based formulations used for ophthalmic drug delivery are hydrogels [13], nanoparticles [14], colloidal systems coated with chitosan [15] etc.
De Campos et al. [14] demonstrated the potential of chitosan nanoparticles with incorporated cyclosporine A in improving the delivery of drugs to the ocular mucosa.
Furthermore, chitosan-based colloidal systems were found to work as trans mucosal drug carriers, either facilitating the transport of drugs to the inner eye or their accumulation into the corneal epithelia. The use of chitosan-based colloidal suspensions in vivo showed a significant increase in ocular drug bioavailability [15, 16].
Calvo et al. [15], for instance, combined the features of polycaprolactone nanocapsules as ocular carriers with the advantages of the cationic mucoadhesive chitosan and poly-L-lysine (PLL) coating. Even though PLL and chitosan displayed a similar positive surface charge, only chitosan-coated nanocapsules enhanced the ocular penetration of indomethacin with respect to uncoated nanocapsules. The authors suggested that an undetermined property of chitosan was responsible for this enhanced uptake.
Genta et al. [16] indicated that acyclovir-loaded chitosan microspheres offer significantly sustained ocular drug release in vivo. According to the authors, in addition to its mucoadhesive properties, chitosan is effective in retarding the rate of drug release.
Nasal drug delivery system
Chitosan, a cationic bioadhesive natural polymer has remarkable influence in augmenting the transport of polar drugs, peptides and proteins across epithelial surfaces was established in various studies. There are two central effects of chitosan delivery systems on nasal mucosa that influence the permeation of drugs across it.
- Firstly, clearance of the formulation from the nasal cavity is abridged by the cations present in the chitosan bind to negatively charged sialic residues tenders excellent mucoadhesive properties consequently lead to prolonged contact time.
- Secondly, its reversible and momentary action on epithelial tight junctions between cells actually steps up the drug transportation paracellularly.
Morphine administered intranasally to humans, as a simple solution, is only absorbed to a limited degree, with a bioavailability in the order of 10%, compared with intravenous administration. Morphine associated with chitosan was rapidly absorbed, with a tmax of ≥15 minutes and a bioavailability of nearly 60%, and can result in a non injectable opioid formulation capable of offering patients rapid and efficient pain relief [17]. Morphologic and histologic evaluation of the rat nasal mucosa following a 2-week daily administration indicated that chitosan produced only mild to moderate irritation [17, 18].
Akbar Bayat et al. [19] studied the effect of insulin-loaded Chitosan nanoparticles on bioavailability of insulin and it was observed that insulin-loaded Chitosan nanoparticles enhanced the nasal absorption of insulin and shown the sustained effect.
In addition, Fisher et al. [20] developed fentanyl nasal spray formulations with pectin, chitosan, and chitosan–poloxamer 188 for clinical evaluation to provide rapid absorption and subsequently increased bioavailability. The study was conducted in 18 healthy adult volunteers and revealed significantly increased systemic exposure as well as reduced times to peak plasma values for all formulations compared with oral transmucosal fentanyl citrate lozenge.
Buccal drug delivery system
Prolonged adherence to the buccal mucosa is the vital requirement of an ideal carrier for efficient buccal drug delivery. Buccal patches, tablets, and gel formulations prepared with chitosan have been effectively delivered the drug unidirectionally into systemic circulation through buccal mucosa.
In another extensive study the chitosan sponges were developed for buccal administration of insulin, exposed efficient unidirectional delivery of insulin and demonstrated its excellent mucoadhesive properties. The promising unique mucoadhesive and absorption enhancing quality of this polymer further confirmed its aptness for the buccal drug delivery [21].
Gels of chitosan (at 1 or 2% concentration), containing 0.1 or 0.2% chlorhexidine gluconate, release the antifungal agent chlorhexidine gluconate for 3 hours; a prolonged release was also observed with film formulations. No lag-time was observed in the release of chlorhexidine gluconate from either gels or films. The highest antifungal activity was obtained with 2% chitosan gel containing 0.1% of the drug [22]. The loading of chlorhexidine into chitosan to improve the anti-microbial activity of the drug was also confirmed by different formulations [23]. An additional antifungal effect was thought to be achieved since chitosan also inhibits the adhesion of Candida albicans to human buccal cells. A 0.5% wt/v solution depressed the fungal adherence on a surface according to the sequence: low Molecular weight (MW) chitosan>phosphorylated chitosan>amorphous chitosan>carboxymethyl chitosan.
The buccal bilayered devices (bilaminated films, bilayered tablets) using a mixture of drugs Nifedipine and Propranolol hydrochloride and chitosan, with or without anionic cross linking polymers (polycarbophil, sodium alginate, gellan gum), demonstrated that these devices show promising potential for use in controlled delivery of drugs to the oral cavity [24].
In another study, the potential of thiolated chitosan for peptide delivery systems via the buccal mucosa was investigated in pigs [25]. The therapeutic peptide PACAP was applied to pigs, and its bioavailability was determined in order to facilitate the treatment of type 2 diabetes. Due to its strong permeation enhancing properties, tablets based on thiolated chitosan raised continuously the plasma level of this peptide drug, allowing therapeutic range levels to be maintained over the whole period of application.
Oral drug delivery system
Oral ingestion of drugs is the most common route of administration, but unfortunately the gastrointestinal tract represents a barrier for absorption of peptides and proteins. Chitosan, displaying enzyme inhibiting and absorption enhancing activity, appears to be a suitable adjuvant for this purpose, and chitosan derivatives have been evaluated to bypass the gastric medium and operate at neutral pH values, such as those found in the intestinal tract [26].
Trimethyl chitosan chloride, at different degrees of quaternization, increases the permeation and/or absorption of neutral and cationic peptide analogs across intestinal epithelia. Mono-carboxymethylated chitosan, a poly ampholytic polymer able to from visco-elastic gels in aqueous environments or with anionic macromolecules at neutral pH values, appears to be less potent than the quaternized derivative. Nevertheless, mono-carboxymethylated chitosan was found to increase the permeation and absorption of low MW heparin across intestinal epithelia. The mechanism by which Trimethyl chitosan chloride enhances intestinal permeability is similar to that of the protonated chitosan; it reversibly interacts with components of the tight junctions, widening the para cellular routes, without permanent damage to the cell membrane and without altering the viability of intestinal epithelial cells [27]. A sustained or delayed ampicillin release can be provided by delivery systems containing such a polymer [28].
Bioadhesive tablets for intraoral drug delivery were prepared by directly compressing a drug with a mixture of chitosan and sodium alginate in weight ratios of 4: 1, 1: 1 and 1: 4, and the adhesion and release characteristics of the prepared systems were evaluated in vitro and in vivo. The plasma concentration curves for the tablet with a 1: 4 chitosan/alginate ratios showed a sustained release 3 hours after administration [29]. The percentage of ampicillin release, embedded in a chitosan matrix was much higher in an acidic solution compared with the phosphate solution, probably due to the gelation properties of the matrix at low pH [28]. The release rate of the drug from the chitosan matrix was slower for beads than granules, thereby offering the possibility of modifying the formulation to obtain the most convenient oral sustained delivery system [28].
Thanou et al. [30], for instance, demonstrated that intra duodenally applied buserelin results in 0.8% absolute bioavailability in rats, whereas co-administrations with trimethylated chitosans resulted in average bioavailability values between 6% and 13%. In contrast, chitosan HCl did not significantly increase the intestinal absorption at pH 7.2.
Colon-specific drug delivery system
Chitosan is a well accepted and a promising polymer for drug delivery in colonic part, since it can protect the active agents from the hostile conditions of the upper gastrointestinal tract and release the entrapped agent specifically at the colon through degradation of the glycosidic linkages of chitosan by colonic microflora [31]. Chitosan can be modified by reacting with succinic and phthalic anhydride to prepare matrices resistant to dissolution under acidic conditions. Improved drug release profiles under basic conditions suggested that these matrices are suitable for colon-specific delivery of orally administered drugs [32].
M. L. Lorenzo-Lamosa et al. [33] proposed the design of microencapsulated chitosan microspheres for colonic drug delivery. He prepared the pH-sensitive multicore microparticulate system containing Chitosan micro-cores entrapped into enteric acrylic microspheres. Chitosan micro-cores in which sodium diclofenac was entrapped and then it was microencapsulated into Eudragit (L-100 and S-100) to form a multi reservoir system have been prepared. In vitro release study revealed no release of the drug in gastric pH for 3 h and after the lag-time, a continuous release for 8-12 h was observed in the basic pH.
Formulation parameters showed significant influence on drug release pattern. Zinc–pectin–chitosan composite microparticles were designed and developed as colon specific carrier [34]. The formulation was prepared at pH 1.5, 1% chitosan, 120 min cross-linking time, and pectin: drug at 3:1 ratio demonstrated colon-specific drug release. Resveratrol was used as model drug due to its potential activity on colon diseases. In vivo pharmacokinetics of the zinc-pectinate particles was compared with the zinc–pectin–chitosan composite particles in rats. Pharmacokinetics study indicated in vivo colon-specific drug release from the zinc–pectin–chitosan composite particles only. Cross-linking solution pH, cross-linking time, and chitosan concentration in the cross-linking solution exhibited major influence on drug release pattern.
Jitendra kawadkar et al. [35] prepared the Chitosan coated microsphere matrix system for the treatment of ulcerative colitis-A. In these studies, the microspheres of Chitosan HCl was directly compressed with the drug 5-aminosalisylic acid (5-ASA), into matrices. These matrices were compressed into tablets or introduced into capsules and coated. The release of 5-ASA from these compressed matrices by the polymer degrading action of the caecal microflora was evaluated in vitro using rat caecal microflora in virtue of the similarity with human intestinal microflora and it provides better release of 5-amino salicylic acid in the colon having ulcerative colitis.
Chitosan capsules containing insulin entered the colon 8 hours after administration, as evaluated by transit time experiments, starting the hypoglycemic effect from that time [36, 37].
Vaginal drug delivery system
Anti-infective drugs incorporated mucoadhesive vaginal formulations based on chitosan have been reported successfully in various literatures substantiated the best qualities of this polymer for the vaginal drug delivery [38, 39]. Apart from the vaginal tablets and films, pH-or temperature-sensitive delivery systems, nanocarriers, and inserts are also in the investigation.
Mucoadhesive vaginal gel based on chitosan for the delivery of lactic acid was exclusively illustrated the polymer's mucoadhesive performance and release profile [40].
Chitosan, modified by the introduction of thioglycolic acid to the primary amino groups of the polymer, embeds clotrimazole, an imidazole derivative widely used for the treatment of mycotic infections of the genitourinary tract. By introducing thiol groups, the mucoadhesive properties of the polymer were strongly improved and this resulted in an increased residence time of the vaginal mucosa tissue (26 times longer than the corresponding unmodified polymer), guaranteeing a controlled drug release in the treatment of mycotic infections [41].
Amal El-kamel et al. [42] prepared CS based vaginal tablets containing metronidazole by directly compressing the natural cationic polymer Chitosan, loosely cross-linked with glutaraldehyde. The batch containing 6% chitosan, 24% sodium alginate, 30% sodium CMC and 20% MCC showed adequate release properties in both media and gave lower values of swelling index compared with the other examined formulations. It also proved to have good adhesion properties with minimum applied weights. Moreover, its release properties (% dissolution efficiency, DE) in buffer pH 4.8, as well as the release mechanism (n values), were negligibly affected by aging. Thus, this formula may be considered a good candidate for vaginal mucoadhesive dosage forms.
In another study, Sandri et al. [43] evaluated the mucoadhesive and permeation enhancing properties of four different chitosan derivatives: 5-methyl-pyrrolidinone chitosan, two low molecular mass chitosans, and a partially re-acetylated chitosan via the vaginal and buccal mucosa using acyclovir as the model drug. Methyl-pyrrolidinone chitosan showed the highest mucoadhesive and permeation enhancing properties in both vaginal and buccal environments. The capability of enhancing the permeation/penetration of acyclovir was decreased by partial depolymerization of chitosan and disappeared after partial re-acetylation. The antimicrobial properties of chitosan, however, might have a negative impact on the vaginal microflora [44]. Its vaginal use for treatment of chronic diseases has therefore to be seen with caution.
Transdermal drug delivery system
Owing to its irreplaceable film forming capacity, penetration enhancing competence without causing much stress to the skin, skin compatibility and good adhesive properties etc. [45, 46], Prompted the researchers to conduct plenteous studies that have been done extensively and reported on the skin permeation ability of the drugs by using this natural biopolymer chitosan. The electrostatic interaction of the positively charged chitosan mediates protracted contact with the epithelium and the negatively charged glycoprotein residues on the cell surface smooth the progress of the passive diffusion results in the successful absorption of the drug into the underlying epithelium [47, 48]. As a penetration enhancer chitosan disrupts the epithelial tight junctions on the skin and facilitates the drug permeation. This epithelial disruption is very brief and within a diminutive period of time altogether it is reversible [49, 50].
Jaleh Varhosaz et al. [51] prepared the gel containing lidocaine (LC) as a local anesthetic agent with three different MW and concentrations of Chitosan for prolonging anesthetic effect of this drug for transdermal delivery. Lecithin was used as permeation enhancer. Viscosity, bio-adhesion, drug release from synthetic membranes, drug permeation through the biological barrier (rat skin) was studied. It was found that by increasing the concentration and MW of Chitosan, there was an increase in both the rate and extent of drug release and was probably because of the increase in repulsive forces between LC and chitosan cations.
Topical systems for controlled delivery of glycolic acid were prepared to optimize the cosmetic properties of the acid, thereby reducing its adverse effects. Two types of liposomes were investigated: the addition of chitosan into the lipidic bilayer during liposome preparation; and coating of already formed liposomes with chitosan [52]. The results showed that liposomes always modulated glycolic acid release and that the best condition to achieve this control was obtained by the liposomal systems in which the glycolic acid/lipid molar ratio was 5: 1. On the contrary, chitosan microspheres are not able to control glycolic acid release, even after cross-linking [52].
Thacharodi and Rao et al. [53–55] reported permeation-controlled transdermal drug delivery systems (TDS) using chitosan. Studies on Propranolol hydrochloride (prop-HCl) delivery systems using various chitosan membranes with different cross link densities as drug release controlling membranes and chitosan gel as the drug reservoir has been performed. The physicochemical properties of the membranes have been characterized and the permeability characteristics of these membranes to both lipophilic and hydrophilic drugs have been reported [53, 54]. In vitro evaluations of the TDS devices while supported on rabbit pinna skin were carried out in modified Franz diffusion cells [55]. The in vitro drug release profiles showed that all devices released prop-HCl in a reliable, reproducible manner. The drug release was significantly reduced when cross linked chitosan membranes were used to regulate drug release in the devices. Moreover, the drug release rate was found to depend on the crosslink density within the membranes. It was observed that the device constructed with a chitosan membrane with a high crosslink density released the minimum amount of drug. This is due to the decreased permeability coefficient of cross linked membranes resulting from the crosslink points.
Gastro retentive drug delivery system
Gastro retentive drug delivery systems increase the retention of a per-oral dosage form in the stomach and offer numerous advantages for drugs exhibiting an absorption window in the GI tract, drugs that are poorly soluble in the alkaline medium (Verapamil), and drugs that are intended for local action on the gastroduodenal wall [56]. Chitosan has a high potential in the development of a successful gastro retentive drug delivery system because it combines both bioadhesion and floating capabilities [57], especially for drugs that are poorly soluble in intestinal medium and readily soluble in acidic medium. Chitosan could be ideal for use in formulations intended to release drugs slowly in the stomach, since the gel formation by cationic chitosan that is pronounced at acidic pH levels results in marked retardant effects on drug release. Orally administered formulations are initially exposed to the acidic milieu of the stomach, especially if they have been administered to subjects in fasted states, in whom gastric pH is likely to range from approximately 1 to 2. Mucoadhesive ability could result in formulations containing chitosan being retained in the stomach. Adhesion would be expected to be particularly marked under the acidic conditions in the stomach, where cationic chitosan would be highly charged.
The chitosan beads can serve as depot reservoir that allows the continuous gradual release of small amounts of Verapamil in solution to the upper part of the small intestine (the main site of absorption), leading to higher and more uniform blood levels of the drug. Thus, reduced adverse effects are highly expected.
Floating hollow microcapsules of melatonin showed gastro retentive controlled-release delivery. Release of the drug from these microcapsules is greatly retarded, with release lasting for 1.75–6.7 h in simulated gastric fluid. Most of the mucoadhesive microcapsules are retained in the stomach for more than 10 h (e. g., Metoclopramide and Glipizide-loaded chitosan microspheres) [58].
In an additional endeavor chitosan granules prepared with prednisolone demonstrated good buoyancy and controlled release when it was added to acidic and neutral media provide evidence of its appropriateness in making such category of formulations [31].
Gene delivery
Chitosan is the most prominent among natural polymer-based gene delivery vectors, due to its biodegradability, biocompatibility, and degradation potential [59]. Chitosan's cationic qualities have the aptitude to interact with negative molecules such as DNA and form complexes, facilitate transfection and inhibit degradation of the same. Chitosan as (safer to other non-viral vectors) non-viral vector for gene delivery put forward quite a few advantages that are not producing endogenous recombination, oncogenic and immunological effects.
Microcapsules containing calf thymus DNA and prepared by interfacial polymerization of chitosan, and alginate microspheres formed by emulsification/internal gelation, were recovered intact from rat feces following gastrointestinal transit. This is the first report of microcapsules or microspheres containing DNA being passed through the gastrointestinal tract with the potential for substantial recovery [60].
In a study by Erbacher et al. [61], formulation of plasmid DNA with chitosan resulted in a homogeneous population of complexes that were stable and had a diameter of approximately 50-100 nm. These complexes were found to effectively transfect HeLa cells, independently of the presence of serum (10%) without the need for the presence of an endosomolytic agent. The gene expression was also observed to gradually increase over time (from 24-96 h). At 96 h, chitosan was found to be 10-times more efficient than polyethylene-imine-mediated transfection.
Roy et al. [62] described an immunoprophylactic strategy using oral allergen-gene immunisation to moderate peanut antigen induced murine anaphylactic responses. Oral administration of DNA nanoparticles synthesized by complexing plasmid DNA with chitosan resulted in transduced gene expression in the intestinal epithelium, thus indicating the probable use of chitosan-DNA nanoparticles in murine anaphylactic responses.
The molecular mass and deacetylation extent of the chitosan, chitosan to DNA/siRNA charge proportion (N/P ratio) and its strength, the chitosan salt form utilized, pH, serum, additives, chitosan/nucleic acid particles preparation process and routes of administration and diverse formulation allied factors influence the transfection efficiency [63].
As the Mw increased, transfection efficiency also improved [64]. Moderate DD increases the transfection efficiency. A pH of 6.8–7.0 is found to be optimum to achieve a high level of transfection [65]. Higher gene transfer efficiency was achieved in HEK293 cells as compared to other cell types [66]. But, the major drawback of chitosan is its low transfection efficiency. Numerous chemical modification like quaternization [67], deoxycholic acid modification [68], galactosylation [69], PEI grafting [70], and thiolation [71] have been carried out by various groups in an attempt to improve transfection efficiency.
Vaccine delivery
Chitosan is a mucoadhesive polymer that is able to open tight junctions and allow the paracellular transport of molecules across mucosal epithelium, and is therefore suitable for the mucosal delivery of vaccines [72]. Chitosan microparticles were able to associate large amounts of Ovalbumin (model vaccine) and diphtheria toxoid (DT). They are not disintegrated in an acidic environment and protect the antigen against degradation by entrapping it into their porous structure [73]. The chitosan microparticles were only taken up by the follicle-associated epithelium (FAE), in which microfold cells (M-cells) are present. This result was from oral delivery studies in mice, in which chitosan microparticles were found to transport associated Ovalbumin into the Peyer's patches [74]. Oral efficacy studies with DT associated to chitosan microparticles demonstrated that they were able to induce strong DT-specific systemic and local immune responses (IgG and IgA titers, respectively) [75]. The amount of neutralizing antibodies in mice vaccinated with DT-loaded chitosan microparticles was also high; the levels were considered to be protective in man.
Chitosan is shown to be a promising candidate in mucosal vaccine delivery for protein vaccines such as Bacillus anthracis [76], diphtheria [77], and influenza [78]. Chitosan derivative trimethylated chitosan/tripolyphosphate/ovalbumin (TMC/TPP/ OVA) nanoparticles have previously been shown to be very effective nasal vaccine carriers. Replacing TPP by CpG as a cross linking agent to obtain TMC/CpG/OVA nanoparticles modulated the immune response towards a Th1 (T helper cell 1) response after nasal vaccination, while maintaining the strong systemic and local antibody responses observed with TMC/TPP nanoparticles. TMC/CpG nanoparticles are therefore an interesting nasal delivery system for vaccines requiring broad humoral as well as strong Th1-type cellular immune responses [79]. In another study, Ovalbumin was encapsulated in alginate-coated chitosan nanoparticles and delivered via the oral route to Peyer's patches [80].
Jain et al. [81] observed high secretory IgA concentrations and better immune response with nanoparticulate vesicular formulation upon oral administration. Chitosan microparticles show suitable in vitro and in vivo characteristics for oral vaccination and are therefore a promising carrier system for this particular purpose. Fluorescently labeled chitosan microparticles can be taken up by the epithelium of murine Peyer's patches. Since uptake by Peyer's patches is an essential step in oral vaccination, these results show that the presently developed porous chitosan microparticles are a very promising vaccine delivery system. Chitosan particles have been described as a potential oral vaccine carrier [82] and transport of these particles by M-cells has been observed. A drawback of chitosan is its water solubility. With a pKa of 6.2, at physiological pH the primary amine groups of chitosan are protonated and, consequently, OVA/chitosan nanoparticles lose their repulsive surface charge and show colloidal instability. The slightly acid environment of the jejunum will promote the stability of chitosan nanoparticles, but as soon as these particles are transported to the sub epithelial space to interact with immune cells, the physiological pH will be deleterious for its stability. Because TMC carries a permanent positive charge, OVA/TMC nanoparticles will not be affected by small pH shifts and may be a more suitable carrier for mucosal vaccination [83]. An intraduodenal immunization study with OVA/chitosan nanoparticles, OVA/TMC nanoparticles, and unencapsulated OVA was performed to analyze the extent and type of immune response elicited.
Commercial application of chitosan
(Table 2) shows commercial applications of chitosan
Table 2: Commercial applications of chitosan [84, 85]
|Fields of application
|Water & waste treatment
|Flocculant to clarify water (drinking water, pools).Removal of metal ions.Ecological polymer (eliminate synthetic polymers).Reduce odors.
|Pulp and paper
|Surface treatment.Photographic paper.Carbonless copy paper.Purification of water wastes, wet-strength improve agent and chitosan-coated papers.
|Medical and pharmaceuticalmaterials
|Bandages, sponges.Blood cholesterol control.Tumor inhibition.Membranes.Dental/plague inhibition.Skin burns/artificial skin.Contact lens.Control release drugs.Bone disease treatment.Surgical sutures.
|Cosmetics & toiletries
|Maintain skin moisture.Treat acne.Improve suppleness of hair.Reduce static electricity in hair.Tone skin.Oral care (toothpaste, chewing gum).
|Enzyme immobilization.Protein separation.Chromatography, cell recovery.Cell immobilization.Electrodes and sensors.
|Defensive mechanism in plants.Stimulation of plant growth.Seed coating.Frost protection.Time release of fertilizers and nutrients into the soil.
|Food & beverages
|Not digestible by human (dietary fiber).Bind lipids (reduce cholesterol).Preservative.Thickener and stabilizer for sauces.Protective, fungistatic, antibacterial.Coating for fruit.
|Sanitary fibrous materials.Surgical threads.Textile material.
|Reverse osmosis.Permeability control.Solvent separation.
|Immunologic.Antitumoral.Hemostatic and anticoagulantHealing.Bacteriostatic.
Chitosan is an abundant natural based polymer, obtained by alkaline N-deacetylation of chitin. The physical and chemical properties of chitosan, such as inter and intramolecular hydrogen bonding and the cationic charge in acidic medium, makes this polymer attractive for the development of conventional and novel pharmaceutical products. So far, a number of chitosan based colloidal systems have been revealed as very promising carriers for bioactive molecules. Being a bioadhesive polymer and having antibacterial activity, chitosan is a good candidate for oral cavity drug delivery. Also, because of its favorable biological properties such as nontoxicity, biocompatibility, and biodegradability, chitosan is a promising candidate for the enhancement of absorption of drugs using a buccal delivery system. Chitosan microspheres can reside longer in the stomach and allow for stomach-specific drug delivery. Chitosan acts as an absorption enhancer in the intestine by increasing the residence time of dosage forms at mucosal sites, inhibiting proteolytic enzymes, and increasing the permeability of protein and peptide drugs across mucosal membranes. Chitosan can be degraded by the micro-organisms, which are present in the colon. Therefore, this polymer could have promising application in a colon-specific drug delivery. A number of in-vitro and in-vivo studies showed that chitosan is a suitable material for efficient non-viral gene and DNA vaccine delivery. As a result of the physical, chemical, and biological properties, chitosan has been used in many different formulations for drug and gene delivery in the gastrointestinal tract.
So going through the applications of chitosan for the beneficial of human being it is not surprising at all to call it a "Multifacet polymer".
Declared None
- Kas HS. Chitosan: Properties, preparation and application to microparticulate systems. J Microencapsulation 1997;14:689–711.
- Paul W, Sharma CP. Chitosan, a drug carrier for the 21st century: a review, STP. Pharma Sci 2000;10:5-22.
- Illum L. Chitosan and its use as a pharmaceutical excipient. Pharm Res 1998;15(9):1326-31.
- Wenshui X, Ping L, Jiali Z, Jie C. Biological activities of chitosan and chit oligosaccharides. Food Hydrocolloids 2011;25:170-9.
- Knorr D. Use of chitinous polymers in food: A challenge for food research and development. Food Technol 1984;38:85-9.
- Shaji J, Jain V, Lodha S. Chitosan: a novel pharmaceutical excipient. Int J Pharm Appl Sci 2010;1(1):11-28.
- Kofuji K, Qian CJ, Nishimura M, Sugiyama I, Murata Y, Kawashima S. Relationship between physicochemical characteristics and functional properties of chitosan. Eur Polym J 2005;41(11):2784-91.
- Averbach BL. Film-forming capability of chitosan. In: Muzzarelli RAA, Pariser ER. editors. Proceedings of the first international conference on Chitin/Chitosan. MIT: Cambridge, MA; 1978. p. 199-209.
- Dhanikula AB, Panchagnula R. Development and characterization of biodegradable chitosan films for local delivery of paclitaxel. AAPS J 2004;6(3):1-12.
- Muzzarelli RAA. Filmogenic properties of Chitin/Chitosan' in Chitin. In: Nature and technology. Muzzarelli RAA, Jeuniaux C, Gooday GW, Eds. Plenum Press: New York; 1986. p. 389-96.
- Park JW, Choi KH, Park KP. Acid-base equilibria and related properties of chitosan. Bull Korean Chem Soc 1983;4(2):68-72.
- Bansal V, Sharma PK, Sharma N, Pal OP, Malviya R. Applications of chitosan and chitosan derivatives in drug delivery. Adv Bio Res 2011;5(1):28-37.
- Gupta H, Velpandian T, Jain S. Ion-and pH-activated novel in-situ gel system for sustained ocular drug delivery. J Drug Targeting 2010;18:499–505.
- De Campos AM, Sanchez A, Alonso MaJ. Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface application to cyclosporine A. Int J Pharm 2001;224:159–68.
- Calvo P, Vila-Jato JL, Alonso MaJ. Evaluation of cationic polymer-coated nanocapsules as ocular drug carriers. Int J Pharm 1997;153:41–50.
- Genta I, Conti B, Perugini P, Pavanetto F, Spadaro A, Puglisi G. Bioadhesive microspheres for ophthalmic administration of acyclovir. J Pharm Pharmacol 1997;49:737–42.
- Dyer AM, Hinchcliffe M, Watts P. Nasal delivery of insulin using novel chitosan based formulations: a comparative study in two animal models between simple chitosan formulations and chitosan nanoparticles. Pharm Res 2002;19(7):998-1008.
- Illum L, Watts P, Fisher AN. Intranasal delivery of morphine. J Pharmacol Exp Ther 2002;301(1):391-400.
- Bayat A, B Larijani, S Ahmadian, HE Junginger, M Rafiee-Tehrani. Preparation and characterization of insulin nanoparticles using chitosan and its quaternized derivatives. Nanomed: Nanotechnol Biol Med 2008;4(2):115-20.
- Fisher A, Watling M, Smith A, Knight A. Pharmacokinetic comparisons of three nasal fentanyl formulations; pectin, chitosan and chitosan–poloxamer 188. Int J Clin Pharmacol Ther 2010;48:138–45.
- Ana Portero, Desire´e Teijeiro-Osorio, Maria J Alonso, Carmen Remun˜a´n-Lo´pez. Development of chitosan sponges for buccal administration of insulin. Carbohydr Polym 2007;68:617–25.
- Senel S, Ikinci G, Kas S. Chitosan films and hydrogels of chlorhexidine gluconate for oral mucosal delivery. Int J Pharm 2000;193(2):197-203.
- Giunchedi P, Juliano C, Gavini E. Formulation and in vivo evaluation of chlorhexidine buccal tablets prepared using drug-loaded chitosan microspheres. Eur J Pharm Biopharm 2002;53(2):233-9.
- Remunan-Lopez C, Portero A, Vila-Jato JL, Alonso MJ. Design and evaluation of chitosan/ethylcellulose mucoadhesive bilayered devices for buccal drug delivery. J Controlled Release 1998;55:143-52.
- N Langoth, H Kahlbacher, G Schöffmann, I Schmerold, M Schuh, S Franz, et al. Bernkop-Schnürch, Thiolated chitosans: design and in vivo evaluation of a mucoadhesive buccal peptide drug delivery system. Pharm Res 2006;23:573–9.
- Bernkop-Schnürch A, Walker G. Multifunctional matrices for oral peptide delivery. Crit Rev Ther Drug Carrier Syst 2001;18(5):459-501.
- Thanou M, Verhoef JC, Junginger HE. Oral drug absorption enhancement by chitosan and its derivatives. Adv Drug Deliv Rev 2001;52(2):117-26.
- Chandy T, Sharma CP. Chitosan matrix for oral sustained delivery of ampicillin. Biomater 1993;14(12):939-4.
- Miyazaki S, Nakayama A, Oda M. Chitosan and sodium alginate based bioadhesive tablets for intraoral drug delivery. Biol Pharm Bull 1994;17(5):745-7.
- M Thanou, BI Florea, MWE Langemeÿer, JC Verhoef, HE Junginger. N-trimethylated chitosan chloride (TMC) improves the intestinal permeation of the peptide drug buserelin in vitro (caco-2 cells) and in vivo (rats). Pharm Res 2000;17:27–31.
- Hejazi R, Amiji M. Chitosan-based gastrointestinal delivery systems. J Controlled Release 2003;89:151–65.
- Aiedeh K, Taha MO. Synthesis of chitosan succinate and chitosan phthalate and their evaluation as suggested matrices in orally administered, colon-specific drug delivery systems. Arch Pharm (Weinheim) 1999;332(3):103-7.
- Lorenzo-Lamosa ML, C Remunan-Lopez, JL Vila-Jato, MJ Alonso. Design of microencapsulated chitosan microspheres for colonic drug delivery. J Controlled Release 1998;52:109-18.
- Surajit Das, Anumita Chaudhury, Ka-Yun Ng. Preparation and evaluation of zinc–pectin–chitosan composite particles for drug delivery to the colon: Role of chitosan in modifying in vitro and in vivo drug release. Int J Pharm 2011;406:11–20.
- Kawadkar J, A Ram. Colon targeted chitosan microsphere compressed matrices for the treatment of ulcerative colitis. Pharm inf Net 2007;5(4).
- Tozaki H, Komoike J, Tada C. Chitosan capsules for colon-specific drug delivery: improvement of insulin absorption from the rat colon. J Pharm Sci 1997;86(9):1016-21.
- Zhang H, Alsarra IA, Neau SH. An in vitro evaluation of a chitosan-containing multiparticulate system for macromolecule delivery to the colon. Int J Pharm 2002;239(1-2):197-205.
- Knapczyk J. Chitosan hydrogels as a base for semisolid drug forms. Int J Pharm 1993;93:233-7.
- Gavini E, Sanna V, Juliano C, Bonferoni MC, Giunchedi P. Mucoadhesive vaginal tablets as veterinary delivery system for the controlled release of an antimicrobial drug acriflavine. AAPS Pharm Sci Tech 2002;3:E20.
- Bonferoni MC, Giunchedi P, Scalia S, Rossi S, Sandri G, Caramella C. Chitosan gels for the vaginal delivery of lactic acid: relevance of formulation parameters to mucoadhesion and release mechanisms. AAPS Pharm Sci Tech 2006;7:5.
- Kast CE, Valenta C, Leopold M. Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole. J Controlled Release 2002;81:347-54.
- A El-Kamel, M Sokar, V Naggar, S Al Gamal. Chitosan and sodium alginate based bioadhesive vaginal tablets. AAPS J 2002;4:224–30.
- G Sandri, S Rossi, F Ferrari, MC Bonferoni, C Muzzarelli, C Caramella. Assessment of chitosan derivatives as buccal and vaginal penetration enhancers. Eur J Pharm Sci 2004;21:351–9.
- D Raafat, H-G Sahl. Chitosan and its antimicrobial potential–a critical literature survey. Microb Biotechnol 2009;2:186–201.
- Shimoda J, Onishi H, Machida Y. Bioadhesive characteristics of chitosan microspheres to the mucosa of rat small intestine. Drug Dev Ind Pharm 2001;27:567–76.
- He P, Davis SS, Illum L. In vitro evaluation of the mucoadhesive properties of chitosan microspheres. Int J Pharm 1998;166:75–88.
- Park Y, Lee Y, Lee J, Seol C, Lee S. Controlled release of platelet-derived growth factor-BB from chondroitin sulfate-chitosan sponge for guided bone regeneration. J Controlled Release 2000;67:385-94.
- Ramanathan S, Block L. The use of chitosan gels as matrices for electrically modulated drug delivery. J Controlled Release 2001;70:109-23.
- Dodane V, Vilivalam VD. Pharmaceutical applications of chitosan. Pharm Sci Tech Today 1998;1:246–53.
- Holme H, Hagen A, Dornish M. Influence of chitosan on permeability of human intestinal epithelial (Caco-2) cell: the effect of molecular weight and degree of deacetylation and exposure time. Adv Chitin Sci 2000;4:259-65.
- Varshosaz J, F Jaffari, S Karimzadeh. Development of bioadhesive chitosan gels for topical delivery of lidocaine. Sci Pharm 2006;74:209-23.
- Perugini P, Genta I, Pavanetto F. Study on glycolic acid delivery by liposomes and microspheres. Int J Pharm 2000;196(1):51-61.
- D Thacharodi, K Panduranga Rao. Propranolol hydrochloride release behavior of cross linked chitosan membrane. J Chem Technol Biotechnol 1993;58:177.
- D Thacharodi, K Panduranga Rao. Release of nifedipine through cross linked chitosan membranes. Int J Pharm 1993;96:33.
- D Thacharodi, K Panduranga Rao. Development and in vitro evaluation of chitosan based transdermal drug delivery systems for controlled delivery of Propranolol hydrochloride. Biomater 1995;16:145.
- Moes AJ. Gastro retentive dosage forms. Crit Rev Ther Drug Carrier Syst 1993;10:143-95.
- Yang L, Eshraghi J, Fassihi R. A new intragastric delivery system for the treatment of helicobacter pylori associated gastric ulcer: in vitro evaluation. J Controlled Release 1999;57(3):215-22.
- CE Kast, C Valenta, M Leopold, A Bernkop-Schnürch. Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole. J Controlled Release 2002;81:347-54.
- Prabaharan M, Mano JF. Chitosan-based particles as controlled drug delivery systems. Drug Delivery 2005;12(1):41-57.
- Alexakis T, Boadi DK, Quong D. Microencapsulation of DNA within alginate microspheres and cross-linked chitosan membranes for in vivo application. Appl Biochem Biotechnol 1995;50(1):93-106.
- Erbacher P, Zou S, Bettinger T, Steffan AM, Remy JS. Chitosan-based vector DNA complexes for gene delivery: Biophysical characteristics and transfection ability. Pharm Res 1998;15:1332-9.
- Roy K, Mao HQ, Huang SK, Leong KW. Oral gene delivery with chitosan-DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat Med 1999 5:387-91.
- Shirui Mao, Wei Sun, Thomas Kissel. Chitosan-based formulations for delivery of DNA and siRNA. Adv Drug Delivery Rev 2010;62:12–27.
- Kiang T, Wen J, Lim HW, Kam KW, Leong W. The effect of the degree of chitosan deacetylation on the efficiency of gene transfection. Biomaterials 2004;25(22):5293-301.
- Sailaja AK, Amareshwar P, Chakravarty P. Chitosan nanoparticles as a drug delivery system. Res J Pharm Biol Chem Sci 2010;1(3):474-84.
- Nydert P, Dragomir A, Hjelte L. Chitosan as a carrier for non-viral gene transfer in a cystic-fibrosis cell line. Biotechnol Appl Biochem 2008:51(4):153-7.
- Germershaus O, Mao S, Sitterberg J, Bakowsky U, Kissel T. Gene delivery using chitosan, trimethyl chitosan or polyethylenglycol-graft-trimethyl chitosan block copolymers: establishment of structure-activity relationships in vitro. J Controlled Release 2008;125(2):145-54.
- Kim YH, Gihm SH, Park CR, Lee KY, Kim TW, Kwon IC, et al. Structural characteristics of size-controlled self-aggregate of deoxycholic acid-modified chitosan and their application as a DNA delivery carrier. Bioconjugate Chem 2001;12(6):932-8.
- Jiang HL, Kim YK, Lee SM, Park MR, Kim EM, Jin YM, et al. Galactosylated chitosan-g-PEI/DNA complexes-loaded poly(organophosphazene) hydrogel as a hepatocyte targeting gene delivery system. Arch Pharm Res 2010;33(4):551-6.
- Wang X, Yao J, Zhou JP, Lu Y, Wang W. Synthesis and evaluation of chitosan-graft-polyethylenimine as a gene vector. Pharmazie 2010;65(8):572-9.
- Zhao X, Yin L, Ding J, Tang C, Gu S, Yin C, et al. Thiolated trimethyl chitosan nanocomplexes as gene carriers with high in vitro and in vivo transfection efficiency. J Controlled Release 2010;144(1):46-54.
- Van der Lubben IM, Verhoef JC, Borchard G, Junginger HE. Chitosan for mucosal vaccination. Adv Drug Deliv Rev 2001;52:139-44.
- Van der Lubben IM, Kersten G, Fretz MM, Beuvery C, Coos Verhoef J. Junginger HE. Vaccine 2003;21(13-14):1400-8.
- Bacon A, Makin J, Sizer PJ, Jabbal-Gill I, Hinchcliffe M, Illum L. Carbohydrate biopolymers enhance antibody responses to mucosally delivered vaccine antigens. Infect Immun 2000;68:5764-70.
- Xu W, Shen Y, Jiang Z, Wang Y, Chu Y, Xiong S. Intranasal delivery of chitosan-DNA vaccine generates mucosal SIgA and anti-CVB3 protection. Vaccine 2004;22(27–28):3603-12.
- Bivas-Benita M, Laloup M, Versteyhe S, Dewit J, De Braekeleer J, Jongert E. Generation of Toxoplasma gondii GRA1 protein and DNA vaccine loaded chitosan particles: preparation, characterization, and preliminary in vivo studies. Int J Pharm 2003;266(1-2):17-27.
- Xie Y, Zhou NJ, Gong YF, Chen J, Zhou XJ, Lu NH, et al. The immune response induced by H. pylori therapeutic vaccine with chitosan as adjuvant. J Gastroenterol Hepatol 2007;22:A239.
- Hasegawa H, Ichinoche T, Tamura S, Kurata T. Development of mucosal vaccine for influenza viruses: preparation for a potential influenza pandemic. Expert Rev Vaccines 2007;6(2):193-201.
- Slutter B, Jiskoot W. Dual role of CpG as immune modulator and physical crosslinker in ovalbumin loaded N-trimethyl chitosan (TMC) nanoparticles for nasal vaccination. J Controlled Release 2010;148:117–21.
- Borges O, Cordeiro-da-Silva A, Romeijn SG. Uptake studies in rat Peyer's patches, cytotoxicity and release studies of alginate coated chitosan nanoparticles for mucosal vaccination. J Controlled Release 2006;114(3):348-58.
- Jain S, Sharma RK, Vyas SP. Chitosan nanoparticles encapsulated vesicular systems for oral immunization: preparation, in-vitro and in-vivo characterization. J Pharm Pharmacol 2006;58(3):303-310.
- Van der Lubben IM, Verhoef JC, Van Aelst A, Borchard G, Junginger HE. Chitosan microparticles for oral vaccination: preparation, characterization and preliminary in vivo uptake studies in murine peyer's patches. Biomaterials 2001;22:687.
- Van der Lubben IM, Konings FAJ, Borchard G, Verhoef JC, Junginger HE. In vivo uptake of chitosan microparticles by murine peyer's patches: visualization studies using confocal laser scanning and immuno-histochemistry. J Drug Target 2001;9:39-47.
- Struszczyk MH. Chitin and chitosan part II. Applications of chitosan. Polimery 2002;47:396-403.
- Rinaudo M. Chitin and chitosan: properties and applications. Prog Polym Sci 2006;31:603-32.
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There are 170 journalists behind bars in Turkey, most of whom were arrested after the coup attempt in July 2016
A Turkish court on Tuesday ruled to keep in jail four staff from Turkey's main opposition daily on terror-related charges, in a controversial case seen as a test for media freedom under President Recep Tayyip Erdogan.
Prosecutors accuse a total of 17 current and former writers, cartoonists and executives from Cumhuriyet ("Republic") of supporting terror groups, charges lambasted by the defence as absurd.
Four of the suspects remained behind bars ahead of Tuesday's latest hearing, with the others now free but still on trial and risking heavy jail sentences if convicted.
The Istanbul criminal court ruled that the four should stay in jail, dashing the hopes of supporters that all the accused could be released ahead of the verdict. The next hearing was set for 25 December.
Dozens of supporters had earlier gathered outside the court in Istanbul, unfurling banners saying: "Stop hunting the opposition and arresting journalists" and "justice for Cumhuriyet".
The 17 are charged with supporting through their coverage three groups Turkey views as terror groups - the Kurdistan Workers' Party (PKK), the ultra-left Revolutionary People's Liberation Party-Front (DHKP-C), and the movement of preacher Fethullah Gulen, blamed by Ankara for last year's failed coup.
The defendants risk up to 43 years in prison if convicted.
The court in July freed seven of the daily's staff after 271 days behind bars, including respected cartoonist Musa Kart and Turhan Gunay, editor of the books supplement.
There is no crime, there is no proof and there is no release.
- Cumhuriyet, Turkish newspaper
Another defendant, one of Turkey's most respected journalists Kadri Gursel, was released last month after spending nearly a year in jail.
But the four who must remain behind bars for at least another two months include some of the biggest names in the Turkish media world.
The paper's chairman Akin Atalay and editor-in-chief Murat Sabuncu have now been held for 366 days while investigative reporter Ahmet Sik has been held for 305 days.
The fourth man, accountant Emre Iper, has been detained for 208 days, and must also remain under arrest.
Since the July 2016 coup attempt, more 50,000 people have been arrested (AFP)
Sik wrote a book exposing the past ties of members of the Turkish elite to the Gulen movement and has angrily denounced Erdogan and his allies at every opportunity in the court.
Addressing the court, Sabuncu vowed Cumhuriyet had not "bowed to pressure and will never do so". Atalay said their "arrest is not based on any legal grounds but a political plan."
"There is no crime, there is no proof and there is no release," the paper wrote bitterly after the ruling was announced.
The trial also resumed Tuesday of celebrated Turkish novelist Asli Erdogan in which she is accused of "terror propaganda" for the PKK on account of her work to the now shut down pro-Kurdish newspaper Ozgur Gundem.
The court ordered its news editor Inan Kizilkaya and the newspaper's licence holder Kemal Sancili to be released on judicial supervision after they were imprisoned for over a year, lawyer Erdal Dogan told AFP.
Erdogan - no relation of the president - faces life in prison if convicted but was released from pre-trial detention in December last year. She did not attend the hearing.
According to the P24 press freedom group, there are 170 journalists behind bars in Turkey, most of whom were arrested after the coup bid. Turkey ranks 155 out of 180 on the latest Reporters Without Borders (RSF) world press freedom index.
Since the July 2016 coup attempt, 50,000 people have been arrested during the state of emergency over alleged Gulen links but opposition media and pro-Kurdish activists have also been caught up in the crackdown. Gulen denies any links to the coup bid.
An Istanbul court last week had ordered the conditional release of eight human rights activists, including Amnesty International's Turkey director Idil Eser, as their trial on contested terror charges continues.

subset: commoncrawl


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Saturday, 19 April 2014
12 comments:
Love the way your pom pom clips match with the shoes :)ReplyDelete
Ah love your trousers! and how your styled them with that jumper!ReplyDelete
Such a lovely I just threw this on but still look amazingg look! This looks a right treat! Aha and happy easter doll enjoy the chocolate whilst you still have an exuse aha!xoReplyDelete
this outfit actually seems so easter-y and lovely! those pants are gorgReplyDelete
omg I love the rainbow sweater and cute little pom pom clips on your shoes! <3ReplyDelete
Love this, the pom pom shoes are perfect <3ReplyDelete
The Quirky Queer
the shoooooooes!ReplyDelete
amazing & cute look! love the platforms and pom poms! xReplyDelete
Zandra // AZTEC DOLL Fashion & Beauty Blog
That is such a cute outfit! LOVE the trousers!ReplyDelete
Another great outfit! :DReplyDelete
Love Cheap Frills x
loving that top!ReplyDelete
Such a cute jumper!ReplyDelete


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Elixir of the old East
Make a mixture of 120 ml of lemon juice, 200 grams of honey and 40 ml of olive oil. Store the resulting mixture in the refrigerator. Consume one tablespoon of the mixture in the morning on an empty stomach. You can give your children one teaspoon of the mixture as well.
Chinese remedy for immunity
Cinnamon is a spice which is very powerful and is widely used in traditional Chinese medicine. It is used as a remedy for colds in combination with tea and fresh ginger. This amazing spice can help with problems linked with the digestive system. It can also help when it comes to regeneratingnervesandblood. You can gain numerous benefits by drinking this drink
Put 2 teaspoons of cinnamon, one tablespoon of honey and one teaspoon of grind ginger in 200 ml of boiled water. Finally, add three tablespoon of lemon juice and cover the bowl you are using. Do this in the evening. Drink half of the resulting mixture before you go to bed. Drink the other half in the morning on an empty stomach.
Indian elixir
Put half a teaspoon of turmeric, three tablespoons of almond oil, two tablespoons of honey and half a cup of water in a cup of goat milk. Mix everything well. Instead of using almond oil, you can use olive oil. You should drink this elixir in the morning on an empty stomach. It is excellent for improving the immune system.
Paranoiac tea
Ancient Egyptians used to often consume hibiscus tea. Of course, they had good reason about it. This tea is rich in antioxidants which protect the skin from aging. Cleopatra used to drink this kind of tea very often in order to rejuvenate her body and soul.
Source: healthyfoodstar.com


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I while back people were asking if others had regular reviews with their doctor so I thought the following may be of interest.
I will be 70 next month, had AF but clear for the last nearly seven years after three ablations, still get occasional bouts of multiple ectopics and short runs of tachycardia but not on any meds for AF other than warfarin with max 84 day tests.. Had prostate cancer in 2011 which was successfully operated on ((full prostatectomy) followed by 33 sessions radiotherapy and three years hormone implants. Now on three monthly PSA watch blood tests . Have a flu jab every year and the old poo sticks tests whenever they come through the post (two years?)
About every six months I am asked to do a seven day blood pressure chart which I send in to the medical centre and am on losartan amd amlodopine for BP plus statin for cholesterol.
Once a year I have blood test for liver and kidney function, cholesterol, blood sugars and a few other bits and pieces and have weight and BMI checks at that time.
I have just received a letter from my old EP at Royal Brompton Hospital with an appointment for July this year. Thinking this may be a mistake I rang his secretary. Early last year I wrote to him regarding a bad bout of ectopics and how we could deal with them but never went up to London to see him and they thankfully stopped after taking a couple of days of medication and a session of Bowen to relax the vagus nerve. EPs secretary told me he just wants to see me to make sure and to catch up on things also to keep me active on the books.
So my point is that some of us are well looked after with considerable after-care but do wonder just how many and how much it depends on a) how well you bond with and work with your doctors and b) how good are the internal systems at your own medical centre.
Discuss! lol


text:
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500 craft beers is our way of professing dedication to your enjoyment. We select the local, the rare, the classic and the trendy so that your snifter, pint or koozie is always teeming with delicious liquid.
Our craft beer is delivered right to our stores so you get the freshest selection around. Visit your local ABC beer haven to browse hundreds of craft beers today!
*Orders on this site containing spirits can be shipped to stores only.
Available for spirits and wine from our delivery partners.
Sku: 297802 1.75L
Bright, fresh and almost effervescent with tinges of candied ginger. Pepper comes through immediately, but soon fades to agave and mint.
Country: MEXICO
Varietal: BLANCO / SILVER


text:
Herban Cowboy® Sport Maximum Protection Dry Spray Deodorant & Body Spray™
Write a Review
Item # 216212
Free shipping available with any purchase over $49. No cash value. Void where prohibited, taxed or restricted by law. Valid at GNC.com or when calling 1-877-GNC-4700. Free shipping offer applies to ground shipping on orders shipped within the continental United States only. Free shipping offer does not include P.O. Boxes and APO/FPO addresses. Free shipping offer does not apply when shipping to Alaska, Hawaii or Puerto Rico. Not valid on previous purchases, exchanges or special orders. No substitutions or backorders. GNC may offer other free shipping offers periodically. Details of these offers will be set forth within the specific promotions. Free shipping offer excludes ready-to-drink products.
Size: 2.8 oz(s)
The product quantity for an item in your shopping cart has exceeded our Maximum Purchasing Policy. Please adjust your quantity to (12) and try again.
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Product Information
DescriptionInstantly dry, clear & confident
Does NOT contain: Aluminum, Triclosan, Parabens, Phthalates, or Chemical Propellants
Vegan/ Cruelty Free/ Not Tested On Animals/ 100% US Made
PRODUCT DIRECTIONS / ADDITIONAl INFOTwist cap to unlock. Spray 4 inches away from body. If dispenser clogs, rinse in warm water.
WarningsSEE MANUFACTURER'S LABEL FOR ADDITIONAL PRODUCT INFORMATION.
Other IngredientsWater (Aqua), Alcohol Denat, Aloe Barbadensis Leaf Juice, Polysorbate 80, Fragrance, Salvia Officinalis (Sage) Leaf Extract, Bisabolol, Allantoin, Zinc, Ethylhexylglycerin, Polysorbate 20, Citric Acid, Proprietary Essential Oil Blend, Rosmarinus Officinalis (Rosemary) Leaf Extract, Carum Petroselinum (Parsley) Leaf Extract
Herban Cowboy
Minneapolis, MN 55424
Minneapolis, MN 55424


text:
hi all,
I get an error message as "Invalid use of Null' when i try to retreive an attribute value from LDAP.
I could not find the reasons for this...
I find this error message when i try to retreive some specific attributes like first name ,last name in LDAP. Also i want to tel that i am successful in retreiving other attribute values.
What could be the reason for this.
Pls help me in sorting out this.


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If you are looking for a quick and easy gift or just a cute notepad….then look no further. Come find out how to make a Starbucks Notebook.
Here are the supplies you will need for this DIY Notebook:
* Starbucks Coffee Sleeve
* Index Cards
* Scissors
* Glue
* Brush
* Clips
For the complete tutorial on how to put this DIY Notepad together watch our quick video-
Head on over to Instructables to learn how to make a cereal box notebook.
Check Our Other Back To School Projects:
Edible Glue Stick Craft
DIY Notebook T Shirt


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I cannot imagine our home without music. Sharing music is an important part of our family life and everyone enjoys it. I think it is very special that we can sit around with our kids, aged 6 – 26, listen together, discuss the music and generally enjoy our unique and eclectic tastes.
I have been lucky enough to team up with Creativ Music ,Western Canada's most unique music facility. They offer a unique combination of music based programs including; Lessons, Pop Star Video Parties, Acapella Groups, Vocal Booth, Ultimate Glee Camp and Weekly Jams along with the latest in musical instruments from leading brands such as Roland, Cort, Boss, D'addario, Planet Waves. You can read more about their fabulous facilities, programs and parties here.
Giveaway Time
Creativ Music are offering my lucky readers the chance to win one of their "Jump Start" packages.
JumpStart is a unique "get started" , "test the waters", "polish some skills", "learn a new song" program at Creativ. The JumpStart program consists of 6 weeks of 30 minutes lessons PLUS the free used of an instrument during the JumpStart program. They offer, voice, piano, guitar and drum lessons in this program all for a budget conscious price of $149.00.
The winner can book the lessons for anytime that works for them or even gift them – so what are you waiting for?
- Open to Canadian Residents only – Creativ Music is located in North Vancouver and travel to their location will be the winners responsibility.
- All entrants must have reached the age of majority in their place of residence
- All times are in PST.
- Contest ends at 11:59pm February 20th 2015
- Contest winner will be drawn randomly from all qualified entries
- Entries that have been found to be incorrect or incomplete will be removed from the final drawing
- Entrants found to be using multiple identities for multiple entries will be disqualified
- Giveaway Tools is used to randomly draw the winner
- The winner will be notified within 24 hours of the end of the giveaway
- The winner has 48 hours from the time the notification email is sent, to respond with their details
- If no response is received within 48 hrs a second winner will be drawn
- The Winners name will be displayed on the Giveaway Tools once confirmation is received
- Closed Giveaways, with winners details will remain posted, under the closed giveaways tab for a period of one year
- The contest sponsor (in this case Creativ Music Centre) is responsible for prize fulfilment
- Void where prohibited


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Our partner in Sao Paulo is the legendary OMiD Academia de Áudio, founded by Omid Burgin.
The first 5-day Master Seminar is scheduled for 2 to 6 February 2015 and will be hosted by
Friedemann Tischmeyer & Omid Burgin.
The picture is actually from the identical looking mixing room. The mastering room looks identical and is a little bit bigger and differently equipped.


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WHITE PLAINS, New York - In the aftermath of Hurricane Maria, Governor Andrew Cuomo has been leading the charge from New York, sending emergency supplies and personnel through the Empire Relief and Recovery Effort.
Another plane full of critical supplies is scheduled to depart Tuesday morning from Westchester County Airport.
Gov. Cuomo has been increasingly critical of what he, along with many Democrats, have called the government's slow response to Puerto Rico. Tuesday afternoon, President Trump will make his first visit to the storm ravaged island to survey the damage up close and receive a briefing about the ongoing relief efforts.
Meanwhile in Aguadilla, a town on Puerto Rico's northwest tip, FDNY firefighters used a Red Cross truck to hand out undistributed supplies to families still without basic needs. In an recent interview with CNN, Governor Cuomo questioned why it's taken so long for critical resources to get in the hands of those who need them most on the island.
"It's not acceptable. You know? There's no debate. The only thing the federal government can say is, 'Well, Puerto Rico wasn't in a position to help. Puerto Rico had problems.' Yes. That's the nature of the beast. That's like the doctor saying, 'Well, you know, the patient was sick.' Yeah. I know the patient is sick," said Cuomo.


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While on vacation a few years back we spent a day at a water park. Not one to relish roller coasters and other such daredevilry, I nonetheless found myself relenting to familial peer pressure and agreeing to a large raft ride several stories high with many a twist and turn, great speed, and, oh yes, much fun (fun?!?).
After standing in line for too long (or not long enough, depending on one's perspective at the given moment), the four of us, me and my husband and two youngest boys, climbed into the raft, grabbed on for dear life and hurtled forward and down the slide. My youngest son, knowing well my unease, nay my dislike, for all things daring and fearsome, yelled assurances to me the whole way down. "We're almost there, Mama! Not much further! I see the end! Hang on, Mama! Hang on! It's almost over!" And he was right. It was, finally, over, and we emerged from the landing pool exhilarated and, despite my initial misgivings, none the worse for wear.
I did not, however, ride again.
These past couple of weeks have felt much like that water ride: I plunge forward, swept away by forces beyond my control, caught on a dipping, twisting ride that will end in a singular, spectacular splash. Twists and turns, absolutely. Ups and downs, to be sure. Fun, you bet. Scary, oh yes, that too. There's no time to think; I barely grab hold and hang on as life barrels me ever forward. I am spinning and surging with the sort of frantic, frenetic frenzy that leaves me breathless, my heart caught between excited exhilaration and fearful dread. My husband and I call assurances to each other over the surrounding din: "It's almost over! I see the end! Hang on!" and sometimes we shout it with an elated fist pump, other times we whisper it with tears filling our eyes and hearts protesting.
Our boy, our firstborn, graduates in a few weeks and moves away from home a couple of months after that. It doesn't seem possible. Wasn't he just in fourth grade? Like last year? Time, it flies.
Oh, wow, what a ride. So much excitement. So much joy. So much to be grateful for. So much to be humbled by. And, yes, so much to do and to decide and to plan. All that plus laundry too.
That line for the ride at the water park seemed so long to me, interminable even. It was hot and miserable; I was hot and miserable. We weren't moving, not very fast, a snail's pace if that, certainly not quickly enough, not by my estimation. To say it was boring was an understatement. I was anxious and impatient, eager to move forward, ready to get it over with already. I didn't like the waiting, not in the least, and looked with great longing toward the cool refreshment of the pool at the end of the slide and even on to the lunch that would follow not long after.
However, we did, finally, make it to the top much more quickly than I anticipated, and then, just like that, the ride was over, all that waiting finally concluded, quick-as-a-blink.
I've spent many a day feeling caught in similar tedium: waiting, wishing for the next stage, bored by the day's mundane ordinariness. I looked ahead with more impatience than eagerness, listless and dull, frustrated by my seeming inertia. I wanted to go and do; instead I thought myself stuck and stranded. Laundry to fold, dishes to wash, lunch to make, supper to cook, books to read, swings to push, diapers to change, more laundry, errands to run, spankings to give, questions to answer, tantrums to quell, and, yes, more laundry. And go to bed and get up the next day and do it all over again. And again.
And now I've made it to the top. I'm crashing forward, I'm hanging on, I glimpse the end rushing toward me, and I know that suddenly, soon, quick-as-a-blink, this part of our lives will be over. As I brace for that spectacular splash and anticipate the joy and exhilaration that will follow, I see what I couldn't see before: how quickly time flies, how precious those ordinary, waiting days were, and how priceless the opportunity, the privilege, was and is.
And I know for sure and for certain I'd do it all over again.


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Kate Middleton & Prince William Visit the Taj Mahal in India
Kate Middleton and Prince William sit on a bench and pose for photos in front of the Taj Mahal on Saturday (April 16) in Agra, India.
The 34-year-old Duchess of Cambridge looked super chic in her Naeem Khan dress and a pair of earrings that cost less than you might have guessed.
Kate's earrings only cost her $7 and she got them at a souvenir shop during her trip to the Tiger's Nest Monastery in Bhutan, according to People.
20+ pictures inside of Kate Middleton and Prince William at the Taj Mahal…


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I wasn't sure where to put this...so here goes. Just looking for some hints/tips/advice here.
I wrote a song that was based on a current television show and am trying to figure out a way to get it to the "powers that be".
First issue is: Is a basic guitar, voice done on my four-track ok? Send a tape or burn to cd?
Second issue: How do I find out who to send it to?
I've done some looking around and I know who the producers of the show are...not sure if it should go to them or not?
So...any advice?


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Event & Party Item
Type: Party Decorations Occasion: Party
Type: Event & Party Supplies
* This is a sting for the special design Vintage style Baby Party Banners.
* Unique Vintage & Kraft Design.
* Color:As picture shown
* Size: Approx. 11 x 15cm / 4.33 x 5.91 inch
* Ribbon length: Approx. 2.4m / 9.45inch
Package Include:
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Product Description
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Weight: 0.074kg (0.16lb.)
Package Size: 15cm x 11cm x 1cm (5.91in x 4.33in x 0.39in)
If you would like to pay by PayPal, you can pay to our PayPal account: firstname.lastname@example.com and email us. Please email us the name of the product, the quantity and other product attributes. The email address is email@example.com. No matter how many goods you buy in one order, the freight you need to pay is only 15 dollars
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100% Money Back Guarantee on each item. Please contact us within 24 hours upon your receipt of the items. A full refund including shipping will be rendered in the event that the item is not as described. The refund will be rendered once the item has been sent back in original condition.
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Excellent delivery time and costIt was a speedy dispatch and product as described
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Hard as I try I can't find a fault with anything.Excellent Service and a prompt exchange when I found that I needed a size smallerVery Prompt Delivery with precise advice as to what time it will arrive.I'm very pleased with my purchase and will certainly look for anything else that I may need from Jules B.
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24 April 2012 <br/> Fantastic quality and service The colour and print were exactly how I wanted. Made a great hoodie for my fiancee, brilliant work by the guys at TShirt Studio. Delivery was spot on too, would definitely use for future gifts.
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Super fast delivery. Great Wellies thank youDelivery was so fast. Very efficient company. Would use again!
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Ashvin Gidwani Productions (AGP) staged the humorous play 'Blame it on Yashraj' at St.Andrews on 18th directed by Bharat Dhabolkar. The show was a huge success with renowned celebrities attending it. 'Blame it on Yashraj' successfully amused the audiences in Hong Kong and in Mumbai, while taking them on a laughter ride.
Speaking about the show, Ashvin Gidwani, MD & Producer, Ashvin Gidwani Productions (AGP) tells us,
"It is my privilege to work with Bharat who is an incredible person. 'Blame It on Yashraj' has been one of our most successful plays and we are extremely pleased that the audiences in Hong Kong have welcomed it. To see the audiences of Mumbai loving the show have also been a humbling experience."
Bharat Dhabolkar shares his thoughts saying,
"I am glad that 'Blame it on Yashraj' was loved by the people of Hong Kong and Mumbai. It is a great achievement for me and my wonderful cast of talented actors. I look forward to continue writing such stories and keep entertaining my audiences."
Actress Vidya Malvade, Director Vivek Vaswani and actress Perizaad Zorabian among other well-known personalities were seen enjoying and loving the show.
The Plot: 'Blame it on Yashraj' is a hilarious story of a Punjabi/Bengali family caught up in the whirlwind of a wedding getting bigger and bigger by the day, when their darling daughter decides to marry a Muslim boy. It's two hours of poking fun at our prejudices, our peculiar behavior in planning a wedding, the invitee lists, the menu, the decor and the constant awareness that you have finally to bow down before the almighty Bollywood!
Cast: Ananth Mahadevan, Jayati Bhatia, Anchal Sabharwal, Punit Tejwani, Smita Hai, Gaurav Sharma, Palash Dutta & Neel Gagdan.
With brilliant performances by the cast and a humorous story 'Blame it on Yashraj' has effectively conquered the hearts of the theatre enthusiasts making it a delightful evening for all.
For bookings write to email@example.com


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All athletics registrations and fees must be completed online. One registration form can be completed for multiple sports. Each child does need to be registered individually.
The Saint James Athletic Program teaches and encourages Christian values as it promotes physical development, athletic skill, team camaraderie, good sportsmanship, and school spirit.
Any student in grades 5-8 may participate in SJS athletics provided the online registration is completed and there is an annual sports physical on file in the school office prior to first practice for the sport. As required by the Archdiocese of Chicago, students who participate in their school's athletic program will not be allowed to participate (no practices, games, meets, etc.) without the complete and submitted physical.
For the majority of sports, SJS competes in the Northwest Suburban Catholic Conference (NWSCC) and plays against 15 area schools, including St. Alphonsus, St. Anne, St. Colette, St. Emily, St. Francis, Holy Family, St. Hubert, Our Lady of the Wayside, St. Mary, Queen of the Rosary, St. Raymond, St. Theresa, St. Thomas and St. Zachary. For more details including standing and school locations, please click Northwest Catholic Conference website and come to cheer on St. James!
For soccer, SJS competes in North Shore Catholic School Soccer League and plays most games in Glenview against 7 schools including Immaculate Conception in Chicago, North Side Catholic Academy in Chicago, Our Lady of Perpetual Hope in Glenview, Queen of All Saints in Chicago, St. Catherine Laboure in Glenview, Our Lady of Mt. Carmel in Chicago, St. Colette in Rolling Meadows.


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In this fast and competitive world it isn't easy being a freelancer, and it isn't easy to get your foot in the door as a translator, especially when you are young and inexperienced.
I was very lucky in that I got to "learn on the job" when Berlin's alternative magazine culture was exploding in the mid-90s and you could still count the number of English native speakers on one hand. I soon became the "go-to" girl in my network of friends and literally learned where to put apostrophes as I went…No, my local comprehensive school education didn't even stretch to explaining what a relative clause or a collective noun is.
When asked to take on the translations for a new fashion magazine back in 2006, I was told that the workload would be split 50/50 (which was fine with me, as it was always deadline-life-on-hold kind of work, racing to that all important print date) and they added, by the by, that all my work would be proofed by another translator, based in Cologne, Paula Hedley. My blood ran cold as I envisaged an older dame, with scraped-back hair and commas for eyebrows slashing away at my flawed work with her lethal red pen.
Every translator is fearful of having their work criticised (I imagine), and let's face it, no one is perfect. And we translators are not exactly a bunch of team players either, very much used to working alone, and relying on no one: we often work without backup; if the schedule is tight, we often toil late into the night, with no one to offload on. If we're lucky, we might have understanding partners who bring us cups of tea, or older children who pat us on the back on their way out, saying "Oh mum, don't worry, you'll get it done in time."
So I was overjoyed to find out that my new compulsory partner in crime was a svelte but cheeky Newcastle lass with a great sense of humour and an ability to give and take criticism or corrections in the loveliest way possible. It was a match made in heaven. She has the down-to-earth language of a true Northerner, with the humour to go with it, and is a dab hand at creating catchy, punchy headlines that make us a hit in the corporate/commercial world when it comes to selling or making an impact, while I sometimes have the la-di-dah vocab of a professor emeritus and can dissect the most slithery of nested German sentences with the exactitude and grace of a skilled chef wielding a sharp knife. She talks me down per WhatsApp if I want to use the word "excoriate" too often, and I adjust her "made of's" and "made from's" with a motherly stroke.
In 2011 we founded Trend Translations together, with the aim of appealing to a wider commercial spectrum, enabling us to take on larger contracts and expand our business as well as giving our fruitful cooperation a face and a professional corporate design. We are now in a position to turn down jobs, or pass them on to others. One key to our success, I am sure, is the fact that we both proof pretty much all of each other's work. Instead of translating, it is easy to transmogrify instead, producing a babbling stream of verbiage, losing perspective with complex academic sentences (do you see where I am going with this…?) or overcomplicating what should be a punchy title for a watch ad or fashion article. And that's when it is worth its weight in gold to have an honest supportive business partner on hand via Skype, email or WhatsApp to let you know when you are overthinking something, or using jargon no one but Stephen Hawking will understand.
It is probably the savviest decision both of us made, reciprocally proofing each other's work (whenever possible) and finding someone to confide in when a particular project is proving difficult, or some nightmare client hits you with some negative feedback. (Yes, this happens to us all at some stage!) Not only is it nice to be able to send someone your evening's efforts and exchange a few words over your morning coffee, but it will improve your work immeasurably.
So here are my tips on how and where to find that person and how to deal with translation partnerships:
Online platforms like proz.com, or Facebook groups like Standing Out and Parents Who Are Freelance Translators, or Watercooler are a great way to meet people online and exchange thoughts. It's nice to have some business banter, and an excellent source of information for CAT tools, but often these people are based far away in other countries and time zones.
Ideally it's nice to meet people IRL, especially if you are looking for a long- term working partnership. Somehow it is always easier to get a feel for someone and their working methods face to face. Having said that, I only met Paula after we'd been working well together for a few years. She lives in Cologne and I live in Berlin. The old-school Translators' Stammtisch (based in Berlin), or groups aimed at expat writers and translators like those organised by The Reader or Transfiction, or bookstores like Curious Fox or Another Country, are all great places to find like-minded folk if you can pluck up the courage to get out from behind your screen and go out into the big, wide world. (I know, I know, it's really hard…)
It's no good trying to team up with someone who loves to sleep in till eleven and thinks deadlines are for fun rather than a must, if you are at your desk by eight every morning and like to hand work in a day early. Someone who translates only part time and spends most of their day out dog sledding somewhere without phone reception or Wi-Fi is not going to make a good emergency backup. If you are a bit of a workaholic, then find someone equally committed. I know with Paula, that in a pinch we can see things through over a tough weekend, powered by nothing but caffeine and amusing comments on each other's proofed documents, and she won't leave me in the lurch. And we can always cover for each other when we're on holiday.
is a must. Especially when you are earning money together or sharing clients. You need to know that you are on the same page when it comes to pricing and make decisions about how to divvy up work if too much comes in. We both have our own personal clients, people we were recommended to directly, but when our agency is approached in a more general way, we share the work, or figure out who is the best fit. Luckily, we tend more toward the "No, you do it if you want to, no you, no YOU!!" style of cooperation than being greedy about it.
It's probably advisable to find someone with similar or at least overlapping areas of expertise. Beware those who say they can work across the board! We have a good network of people specialising in areas we don't have a clue about (legal or medical texts) and Paula and I overlap on fashion, our main focus, with me specialising more in the direction of textiles, architecture and history, and her veering more toward marketing, tourism and lifestyle.
It's important to communicate clearly, especially when business is on the line. Telling someone exactly when you expect a piece of work back is so much better for all concerned instead of saying "Some time next week would be good," and assuming they have the same "I'll-do-it-right-now" work ethic as you, and then getting pissed off when they send it to you Friday night at 9pm. Paula usually writes something like "Please send back by 2pm" in the header so that I can keep track of her requests during a busy day doing other work. I am often quite random in my "desk time" being a mother of two and fond of heading out to the country, so I try to check in with her regularly and let her know roughly when she can expect me to be around.
Sometimes you have to be nudged into being a little more assertive on the market. I was toddling along quite nicely on our tiny prices, living in Berlin with cheap rent and low expectations, so it took Paula's cool business nous to suggest (gently) that we could start charging more. I almost fell off my chair when she suggested the new pricing, but now I am enthusiastically charging healthy prices that make me even happier to be working in such a fun job, and our clients still get a good deal because being a small agency we don't have high overheads or a large bureaucracy to feed.
It's important to appreciate the person you are working with, even if you don't see them. Being Brits a long way from home, we share a love of British food, a good pie and chips, or a chicken jalfrezi (living in Berlin that counts as British food!) and so on our birthdays or after a particularly hard slog Paula sends me little care packages filled with goodies from Marks & Sparks like biscuits and tea bags. Just another reason why having a partner makes working more fun.Now, who could ask for more from a business partner?! What are you waiting for?
Useful Addresses
Parents who are Freelancers
Standing Out
Another Country Berlin
Curious Fox:
The Reader


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Indelible You! Making Your Mark: Young Artists and Writers Workshops
Against the backdrop of SVMA's summer exhibition, Akin: Nicole and Marc Katano, workshop participants blend two artistic disciplines: visual art and creative writing.
Writer Kate Williams and artist Walt Williams facilitate this popular summer program for youth who have begun to develop a sincere interest in visual art and/or creative writing. Making use of a synergistic, cross-curricular approach, participants engage in a range of art disciplines to inspire their writing, and thematic forms of writing to motivate art making. Photographer Nicole Katano and painter Marc Katano join the July session as guest artists.
July 15–19, 10am–3pm
Ages 10–12 and 13–15
Art Themes: Abstract Painting and Drawing, Photography
Writing Themes: Autobiography, Aspiration, Observation
Limited to 20 students per session


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A big well done to our PADI IDC candidates! Downbelow Managing Director and resident PADI Platinum Course Director Richard Swann was on hand to witness PADI Instructor Examiner Marc van der Poel congratulate each one of them and present their certificates.
For Downbelow, this was the last scheduled PADI IDC for the year 2013 and we look forward to the next round of PADI IDC's in Asia in the year 2014.
If you want to live the diving dream and not get stuck in a boring 9 to 5 job & stuck behind the desk, then act now!
Contact us today on how you can get mentored by Richard and his GoPRO team! You can also refer to our 2014 IDC Asia schedule here.
We'll be waiting for your call!


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Halsey, ORph: firstname.lastname@example.com
If you're interested in learning more about Herrenstolz German Shepherds or the availability of puppies, please contact:
Eleanor Wetgen
Please call or email us to schedule an appointment and get detailed directions.
Turn west on to American Dr from 99E, in about 2.4 miles turn right on to Creek Bend Dr. at the sign. Then proceed 0.5 mile to the next sign at Herrenstolz German Shepherds and you are there.
To get driving directions to Halsey, OR, click on the link below the map.


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How to Remove WannaCry Virus Ransomware From PC
A new ransom-virus namely WannaCry Virus Ransomware has been recently detected by malware researchers that is extremely dangerous. This very ransom-virus is also known as WCry, WNCry, WannaCry, and WanaCrypt0r. According to a reports by security analyst, WannaCry Virus began affecting computers worldwide on 12 May 2017, and in little time affected thousand of Windows PCs across globe. Reports also says, till dated WannaCry Virus Ransomware infecting over 75,000 computers among 99 countries, and demand ransom payments in 20 languages. On depth analysis experts found that WannaCry Virus use EternalBlue exploit, that has been allegedly developed by the U.S. National Security Agency, in order to attack computers running on Microsoft Windows operating systems.
Some popular attack by the WannaCry ransom-virus is Telefónica and some other large companies located in Spain. Along with has targeted parts of the British National Health Service (NHS), FedEx and Deutsche Bahn. Additionally security researchers found over 1,000 computers at Russian Interior Ministry, the Russian Emergency Ministry as well as the Russian telecommunications company MegaFon, has been infected. It is spread widely over Internet and mostly it comes inside your PC through spam email or bundled with free download. Clicks to malicious links spread over social media webpage and sharing data using infected drives are counted as major intrusion methods.
Soon after coming inside the PC, WannaCry Virus Ransomware do complete scan of compromised PC to find out file liable to be encrypted. After collecting them, making use of AES and RSA encryption algorithms encrypt the victims data after which you are unable to access them. Affected computer files can be easily identified as it appends .wcryt, .wncry, .wcry, or .wncrrytt file extensions to each of encrypted files. Following sucessful encryption WannaCry Virus drops @Please Read [email protected] named ransom note onto victim's desktop notifiying them about current situation and asking them to make payment. Currently WannaCry demands for 300 US dollars per computer in bitcoin. Data are important anyway but you don't need to pay to cyber criminals as you may be cheated. Inspite you are strongly recommended to make use of easy to use and reliable Free Scanner tool to get rid of WannaCry Virus Ransomware completely.


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The Bush Administration and the Chinese Government are off the hook, at least for now. The Fair Currency Alliance (FCA), of which AMT is a leading member, has decided against filing a Section 301 (of the Trade Act of 1974) petition that would charge the Chinese Government with violating World Trade Organization rules by significantly undervaluing its currency, the yuan, to gain a trade advantage. The FCA reluctantly came to this conclusion, but realized that holding the Section 301 petition in abeyance and working cooperatively with the Bush Administration was the sensible course to take — at least in the short run.
Currently, the Chinese Government is holding more than $400 billion — equal to one-third of China's Gross Domestic Product — in currency reserves, almost all of which is in U.S. dollar instruments. To soak up the dollars, the Chinese Central Bank has been forced to print even more yuan, or renmimbi. This, in turn, has forced the already hot Chinese economy, which has been growing at a rate of more than 9% per year, dangerously close to the breaking point. Moreover, China's desperate attempt to take U.S. dollars off the market, with the goal of keeping its currency undervalued, is evident in the costly, high-risk dollar-buying strategy that it is currently practicing. Amongst other things, this practice overloads the U.S. Government with hundreds of billions of dollars in low-cost loans as the Chinese buy short-term Treasury bills to store as reserves.
Obviously, this can't go on for long before the entire international monetary-trading system is distorted. Concern over this matter was one of the FCA's main motivations in considering the Section 301 petition. The current situation is causing unfair trade conditions and distorting investment decisions, as U.S. and foreign companies and investors flock to China to take advantage of the abnormally low-cost manufacturing platform created by that undervalued currency. Furthermore, China's hyper-growth in recent months has dramatically affected the commodity markets, as cement, steel scrap, copper, and petroleum are drawn into the rapidly growing industrial powerhouse. The FCA estimates that the Chinese currency is 40% undervalued, and in recent years, both the World Bank and The Economist have provided estimates of even greater disparity. Whatever the exact number, this problem must be addressed with the utmost urgency.
For the time being, the FCA is willing to work with the Bush Administration, which has engaged the Chinese Government over the past year to redress the undervaluation problem. FCA members, and their supporters in Congress, will be patient as the Administration helps the Chinese to undertake a revaluation — either in the form of a re-pegging of their currency in relation to the dollar, or as a modified currency float.
We agree with the Bush Administration that there are many reasons why this revaluation would be in China's own interest, but our patience — and that of the U.S. Congress — is running out. If no action is forthcoming, the filing of the Section 301 petition, or even harsher Congressionally initiated action, will likely occur this year.
By Dr. Paul Freedenberg Vice President-Government Relations AMT The Association For Manufacturing Technology