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®. 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 ∼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® formulation after 24, 48, 72, 96 h treatment, respectively at 0.25 μg/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®. 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® 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® formulation.