Thiolated chitosan nanoparticles for augmented oral bioavailability of gemcitabine: Preparation, optimization, in vitro and in vivo study

Abstract

This study aimed to optimize the synthesis of gemcitabine (Gem) loaded thiolated chitosan nanoparticles (Gem-TCh-NPs) for augmented oral bioavailability by using the superior mucoadhesion property of thiolated Chitosan (TCh). Here, Gem-TCh-NPs were prepared by ionic gelation method, optimized by the design of experiments and evaluated for in vitro and in vivo studies. The optimized formulation exhibited a smaller particle size (180.5 ± 2 nm) along with higher encapsulation efficiency (60 ± 4%) and exhibited a biphasic release pattern. The formulation showed an initial burst followed by sustained release up to 96 h. Further, ~1.2-fold higher mucoadhesion, 4.34-fold higher effective permeation, and 50 times enhanced cytotoxicity as compared to native Gem was achieved. In vivo pharmacokinetic analysis demonstrated ~3 fold higher AUC than Gem (i.v.) and a ~1.2-fold rise in the in contrast to the native Gem (oral). In conclusion, Gem-TCh-NPs could be effective, viable, and promising formulations for augmented oral therapy.