Development and Evaluation of High Oxaliplatin Loaded CS-g-PNIPAAm Co-Polymeric Nanoparticles for Thermo and pH Responsive Delivery

Background: Chitosan-g-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) co-polymer was reported as a much efficient drug carrier but it shows very low percentage of drug loading in to the nanoparticles. Objective: The objective of the present study was to develop highly loaded pH and thermo responsive CS-g-PNIPAAm co-polymeric nanoparticles for tumor specific oxaliplatin delivery. Methods: CS-g-PNIPAAm co-polymer was synthesized by surfactant free dispersion copolymerization method and characterized for its structure (FTIR1H NMR), morphology and lower critical solution temperature (LCST). Different drug loading approaches like direct drug loading during polymerization and self-assembly methods were used. In direct drug loading method the chitosan concentration was varied and in self assembly method the polymer ratio and sonication time were varied for study. Drug loaded nanoparticles were evaluated for particle size, zeta potential, percent drug loading efficiency, percent drug content and in-vitro drug release study. Results: It was observed that, self-assembly method give a high amount of oxaliplatin loaded nanoparticles. Further, in direct loading method, as the concentration of chitosan in co-polymer increases, the percent drug loading and drug release at above LCST of copolymer also increases. Nanoparticles prepared by self assembly method (F-5) showed the maximum drug release at above LCST (pH 7.2) and trace amount of drug release below LCST (pH 7.5), indicating thermo and pH responsive delivery of oxaliplatin. Conclusion: In conclusion, higher oxaliplatin loading can be achieved by using self-assembly method with sonication time 5 min and drug:polymer ratio of about 3:10 and oxaliplatin release can be controlled by varying chitosan concentration in co-polymer