Paclitaxel-loaded poly(γ-glutamic acid)-poly(lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer

Abstract

The study was to develop paclitaxel-loaded formulations using a novel type of self-assembled nanoparticles (P/NPs) composed of block copolymers synthesized by poly(γ-glutamic acid) and poly(lactide). For the potential of targeting liver cancer cells, galactosamine was conjugated on the prepared nanoparticles (Gal-P/NPs). In the in vitro studies, it was found that both the P/NPs and the Gal-P/NPs had a similar release profile of paclitaxel. The activity in inhibiting the growth of HepG2 cells by the Gal-P/NPs was comparable to that of a clinically available paclitaxel formulation (Phyxol®), while the P/NPs displayed a significantly less activity (p<0.05). The biodistribution and anti-tumor efficacy of the prepared nanoparticles were studied in hepatoma-tumor-bearing nude mice. It was found that the groups injected with Phyxol®, the P/NPs or the Gal-P/NPs significantly delayed the tumor growth as compared to the control group injected with PBS (p<0.05). Among all studied groups, the group injected with the Gal-P/NPs appeared to have the most significant efficacy in the reduction of the size of the tumor. This is because a large number of the Gal-P/NPs were observed at the tumor site, and subsequently released their encapsulated paclitaxel to inhibit the growth of the tumor. The aforementioned results indicated that the Gal-P/NPs prepared in the study had a specific interaction with the hepatoma tumor induced in nude mice via ligand-receptor recognition. Therefore, the prepared Gal-P/NPs may be used as a potential drug delivery system for the targeted delivery to liver cancers. © 2005 Elsevier Ltd. All rights reserved.