In vitro and in vivo studies on vitamin E TPGS-emulsified poly(D,L-lactic-co-glycolic acid) nanoparticles for paclitaxel formulation

This work shows a full spectrum of research on Vitamin E TPGS-emulsified Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for paclitaxel formulation to improve its therapeutic index and to reduce the adverse effects of adjuvant Cremophor EL in its current clinical formulation of Taxol(R). Paclitaxel-loaded PLGA NPs were prepared by a modified solvent extraction/evaporation technique with vitamin E TPGS as emulsifier. The formulated NPs were found in quite uniform size of similar to 240 nm diameter. The in vitro drug release profile exhibited a biphasic pattern with an initial burst followed by a sustained release. In vitro HT-29 cell viability experiment demonstrated that the drug formulated in the NPs was 5.64, 5.36, 2.68, and 1.45 times more effective than that formulated in the Taxol(R) formulation after 24, 48, 72, 96 h treatment, respectively at 0.25 mu g/mL drug concentration, which should be even better with the sustainable release feature of the NPs formulation considered. In vivo PK measurement confirmed the advantages of the NP formulation versus Taxol(R). The area-under-the-curve (AUC) for 48 h for Vitamin E TPGS emulsified PLGA NP formulation of paclitaxel were found 3.0 times larger than that for the Taxol(R) formulation. The sustainable therapeutic time, at which the drug concentration drops below the minimum effective value, for the NP formulation could be 1.67 times longer than that for the Taxol(R) formulation. (C) 2005 Elsevier Ltd. All rights reserved.