Design characterization and in vitro in vivo evaluation of paclitaxel loaded nanoparticulate system

Abstract

Novel delivery systems with selective distribution are need of the time for enhanced therapeutic efficacy with no or lesser side effects and with better patient compliances. The objective of the present research work was formulation and characterization of Paclitaxel loaded polymeric nanoparticulate drug delivery system to improve the therapeutic efficacy and selective distribution of Paclitaxel. Paclitaxel loaded nanoparticles were prepared using biodegradable and biocompatible poly caprolactone, poly (lactic-co-glycolic acid) and poly lactic acid polymers. As simple, sensitive and accurate analytical methods are essential for design of delivery systems. UV-spectrophotometric, liquid chromatographic analytical and bioanalytical methods for Paclitaxel was developed and validated in required matrix. The developed methods were simple, selective, sensitive, accurate and precise in the estimation of Paclitaxel. The analytical method was applied in the estimating of Paclitaxel in nanoparticles and in the in-vitro dissolution sample and the bioanalytical method was used to estimation Paclitaxel in plasma, liver, kidney and spleen samples in pharmacokinetic and biodistribution studies. Before formulation, preformulation studies were performed to establish necessary physicochemical properties of Paclitaxel to develop efficient formulation. The bulk characterization, partition coefficient, solubility, stability and compatibility of Paclitaxel with excipients were studied. Paclitaxel is white crystalline powder and its solubility was less than 1 and#956;g/mL. Paclitaxel was stable in pH 1.2 to 7.4, but it undergoes rapid degradation in pH 11.00 with high degradation rate constant. Paclitaxel was compatible with all the polymers and stabilizers used in the formulation of nanoparticles. newlinePaclitaxel loaded poly caprolactone, poly (lactic-co-glycolic acid) and poly lactic acid nanoparticles were prepared using nanoprecipitation and solvent evaporation method. The prepared nanoparticles were characterized for the size, size.