Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation

The purpose of this study was to develop Cremophor® EL-free nanoparticles loaded with Paclitaxel (PTX), intended to be intravenously administered, able to improve the therapeutic index of the drug and devoid of the adverse effects of Cremophor® EL. PTX-loaded PEGylated PLGA-based were prepared by simple emulsion and nanoprecipitation.The incorporation efficiency of PTX was higher with the nanoprecipitation technique. The release behavior of PTX exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release. The in vitro anti-tumoral activity was assessed using the Human Cervix Carcinoma cells (HeLa) by the MTT test and was compared to the commercial formulation Taxol® and to Cremophor® EL. When exposed to 25 µg/ml of PTX, the cell viability was lower for PTX-loaded nanoparticles than for Taxol® (IC50 5.5 vs 15.5 µg/ml). Flow cytometry studies showed that the cellular uptake of PTX-loaded nanoparticles was concentration and time dependent. Exposure of HeLa cells to Taxol® and PTX-loaded nanoparticles induced the same percentage of apoptotic cells. PTX-loaded nanoparticles showed greater tumor growth inhibition effect in vivo on TLT tumor, compared with Taxol®. Therefore, PTX-loaded nanoparticles may be considered as an effective anticancer drug delivery system for cancer chemotherapy.