Enhanced Oral Bioavailability of Paclitaxel Formulated in Vitamin E-TPGS Emulsified Nanoparticles of Biodegradable Polymers: In Vitro and In Vivo Studies

This work evaluates the effects of paclitaxel loaded polymeric nanoparticles (NPs) composed of poly(D,L-lactic-co-glycolic acid) (PLGA) with vitamin E TPGS as emulsifier for oral chemotherapy. NPs prepared by a modified solvent extraction/evaporation technique were observed in spherical shape of 200-300 nm diameter with a high drug encapsulation efficiency (EE) of 80.9%. The TPGS-emulsified PLGA NPs formulation of paclitaxel was found of great advantages over that of Taxol®. The in vitro viability experiment showed that the NP formulation could be 1.28,1.38,1.12 times more effective than Taxol® after 24, 48, 72 h incubation with MCF-7 human breast cancer cell line at 2.5 μg/mL paclitaxel concentration. In vivo evaluation confirmed the advantages of the TPGS-emulsified PLGA NP formulation versus Taxol® in promoting oral bioavailability of paclitaxel. Such a NP formulation achieved more than 10 times higher oral bioavailability than Taxol®, which resulted 9.74-fold higher therapeutic effect and 12.56-fold longer sustainable therapeutic time than Taxol®. The present proof-of-concept experimental data proved that the formulation of vitamin E TPGS emulsified PLGA NPs is a promising approach for paclitaxel oral administration. Oral chemotherapy by NPs formulation is feasible. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3552-3560, 2010