Controlled preparation and antitumor efficacy of vitamin E TPGS-functionalized PLGA nanoparticles for delivery of paclitaxel

Vitamin E TPGS-functionalized polymeric nanoparticles have been developed as a promising drug delivery platform in recent years. Obtaining reproducible monodisperse TPGS/polymeric nanoparticles with high encapsulation efficiency (EE%) still remains a big challenge. In this study, an inverse-phase nanoprecipitation method was developed to synthesize TPGS-functionalized PLGA nanoparticles (TPNs) for controlled release of paclitaxel (PTX). To take advantages of lipids, a part of TPGS in the TPNs was replaced by lipids. The results showed that with weight ratio of TPGS-to-PLGA of 2–3 and a molar replacement of lecithin ratio of 30%, the PTX-loaded TPNs (PTPNs) and PTX-loaded lipid-containing TPNs (PLTPNs) exhibited controllable and nearly uniform size of 130–150 nm and EE% of over 80%. Compared to Taxol®, both the PTPNs and PLTPNs significantly increased the intracellular uptake and exerted strong inhibitory effect on human lung cancer A549 model cells. Furthermore, a selective accumulation to tumor site and significant antitumor efficacy of TPNs in the A549 lung cancer xenografted nude mice were observed by intravenous administration, especially for the PTPNs group. Our data suggested that the inverse-phase nanoprecipitation method holds great potential for the fabrication of the paclitaxel-loaded TPNs and the TPNs prepared here is a promising controllable delivery system for paclitaxel.

Graphical abstractPaclitaxel-loaded TPGS-functionalized PLGA nanoparticles (PTPNs) with controllable and nearly uniform size of 130–150 nm and EE% of over 80% were successfully synthesized by a modified inverse-phase nanoprecipitation method. Compared to Taxol® and the lipid-containing PTPNs, the PTPNs prepared showed stronger antitumor efficacy in vitro and in vivo.Figure optionsDownload full-size imageDownload high-quality image (124 K)Download as PowerPoint slide