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PREPARATION AND CHARACTERIZATION OF ALGINATE CHITOSAN CROSSLINKED NANOPARTICLES BEARING DRUG FOR THE EFFECTIVE MANAGEMENT OF ULCERATIVE COLITIS

Objective: Delivery of anticancer molecule to the liver remains a “holy grail” in molecular medicine and nanobiotechnology with conventional therapy, as conventional cancer chemotherapy does not prove effective as drug molecule does not reach to the target site at therapeutic concentration. Tumor vasculature differs from the vasculature of normal tissue both in morphology and biochemistry. Most of these differences appear too related to angiogenesis (formation of new blood vessels from pre-existing ones). For the present study nanoparticles (NPs) were chosen as a delivery system, because they have many advantages, e. g. they can pass through the smallest capillary vessels because of their ultra-tiny volume, can penetrate cells and tissue gap to arrive at, pH, ion and/or temperature sensitivity of materials, can improve the utility of drugs and reduce toxic side effects. 
Methods: PLGA (poly lactide co glycolic acid) was used for the preparation of NPs because of its biodegradability and biocompatibility. It degrades by hydrolysis of ester linkages in the presence of water in to two monomers lactic acid and glycolic acid. There are a number of ligands available for hepatic delivery, among them lactobionic acid (containing galactose moiety) was selected for present work. Preparation of plain nanoparticles was carried out using emulsification–diffusion method. Optimization of the polymer concentration is the first step during the study and it was performed by varying the polymer concentration where as keeping other variables constant. The prepared formulation was optimized on the basis of particle size and polydispersity index. Amount of drug was optimized on the basis of particle size and percentage entrapment efficiency. 
Results: Particle size and zeta potential of the nanoparticle were determined by zetasizer showed that particles are in nano range (blow 200 nm) and have acceptable range of zeta potential. Shape and surface morphology were determined by TEM and SEM analysis. The conjugation of lactobionic acid with PLGA polymer was proved by FTIR. The in vitro release profiles of entrapped drug from formulations were determined using dialysis membrane. For stability studies, the LDNPs (conjugated NPs) are stored at the temperatures 4±1 °C and room temperature. Human hepatoma cell line HepG2 by SRB assay was selected and it clearly suggests a dose dependent cytotoxicity response i.e. decrease in cell survival fraction with increasing concentration of drug. The in vivo study are important in evaluating the targeting efficacy of designed dosage form and also helps in establishing the correlation between the results obtained from in vitro experimentation to that from in vivo studies. The formulations were administered by tail vein to mice of four groups Group I: PBS 7.4 (control); Group II: 5-FU solution; Group III: DNPs; Group IV: LDNPs. 
Conclusion: The proposed targeting strategy is expected to enhance the therapeutic index of conventional anticancer drug as well as reduce its cytotoxic effects to normal cells.