Tenofovir disoproxil fumarate loaded PLGA nanoparticles for enhanced oral absorption: Effect of experimental variables and in vitro, ex vivo and in vivo evaluation.

In this study, PLGA based nanoparticles of tenofovir disoproxil fumarate (TDF) were designed for enhancing its oral absorption. To develop PLGA based TDF nanoparticles with the goal of minimum particle size and maximum entrapment efficiency statistical optimization techniques (factorial design and response surface methodology) were employed. The optimized nanoparticles were characterized for size, shape, charge and physical state. Further, the stability, cytotoxicity and metabolic protective effect of the nanoparticles were evaluated. Single dose pharmacokinetic study in rats was conducted to evaluate the oral absorption of the designed nanoparticles. Ex vivo everted gut sac studies were performed to evaluate the role of active uptake mechanisms in the absorption of the designed nanoparticles. The results showed that the statistical models employed could determine the interaction effects of the critical factors which were used in the optimization of the nanoparticles. The optimized nanoparticles with a particle size of 218±3.85nm and an entrapment efficiency of 57.3±1.6%. The nanoparticles were able to increase the AUC of tenofovir by 5.8 fold. It was observed that active uptake mechanisms predominantly via clathrin-mediated uptake played a key role in increasing the oral absorption of TDF.