Preparation and In Vitro/Vivo Evaluation of Folate-conjugated Pluronic F87-PLGA/TPGS Mixed Nanoparticles for Targeted Drug Delivery

Abstract

Folate-conjugated Pluronic F87-poly(lactic-co-glycolic acid) block copolymer (FA-F87-PLGA) was synthesized to encapsulate anticancer drug Paclitaxel (PTX) for targeted drug delivery. To further improve the curative effect, D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS or Vitamin E TPGS) was added to form FA-F87-PLGA/TPGS mixed NPs. FA-F87-PLGA was synthesized by the ring-opening polymerization and the structure was characterized. PTX-loaded nanoparticles were prepared with the nanoprecipitation method. The physicochemical characteristics were studied to determine the appropriate dose ratio of the FA-F87-PLGA to TPGS. The cytotoxicity against Ovarian Cancer Cells (OVCAR-3) was determined by MTT assay. The Area-Under-the Curve (AUC) and half-life were measured in the vivo pharmacokinetic studies. Based on the optimization of particle size and embedding rate of PTX-loaded mixed NPs, the appropriate dosage ratio of FA-F87-PLGA to TPGS was finally determined to be 5:3. According to in vitro release studies, the cumulative release rate of PTX-loaded FA-F87-PLGA/TPGS mixed NPs was 92.04%, which was higher than that of nanoparticles without TPGS. The cytotoxicity studies showed that the IC50 value of PTX-loaded FA-F87-PLGA/TPGS decreased by 75.4 times and 19.7 times after 72 h treatment compared with free PTX injections and PTX-loaded FA-F87-PLGA NPs, respectively. In vivo pharmacokinetic studies indicated that FA-F87-PLGA/TPGS mixed NPs had a longer drug metabolism time and a larger Area-Under-the-Curve (AUC) compared with free PTX injections. FA-F87-PLGA/TPGS mixed NPs are potential candidates for targeted drug delivery systems.