Pharmacokinetics and in vivo biodistribution of optimized PLGA nanoparticulate drug delivery system for controlled release of emtricitabine.

The objective of this study was to develop systematically optimized (OPT) nanoparticles (NPs) providing a controlled release using PLGA of emtricitabine (FTC) employing Formulation by Design (FbD), and evaluate their in vitro and in vivo performance. FTC generates severe adverse effects with risks of toxicity. Thus, NPs were prepared to reduce these drawbacks in this study. The NPs were prepared by water-in-oil-in-water (w/o/w) emulsion method, followed by high-pressure homogenization. The FTC NPs were systematically OPT using 3(2) central composite design and the OPT formulation located using overlay plot. The pharmacokinetics and in vivo biodistribution of OPT-FTC NPs were investigated in male Wistar rats via the oral administration. Transmission electron microscopy studies on OPT-FTC NPs demonstrated uniform shape and size of particles. In vitro release was sustained up to 15 days in PBS pH 7.4. Augmentation in the values of Cmax (1.63 fold) and AUC0-∞ (5.39 fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT-FTC NPs compared to pure drug. OPT-FTC NPs showed 2.325 fold increase in the values of FTC concentrations in liver. The OPT-FTC NPs was found to be quite stable during 6 months of study period. Hence, the developed OPT-FTC NPs can be used as drug carrier for sustained/prolonged drug release and/or to reduce toxic effects.