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

• Published in: Biomaterials 2006-03, Vol.27 (9), p.2051-2059
• Main Authors: Liang, Hsiang-Fa, Chen, Chiung-Tong, Chen, Sung-Ching, Kulkarni, Anandrao R., Chiu, Ya-Ling, Chen, Mei-Chin, Sung, Hsing-Wen
• Format: Article
• Language: English
• Subjects: Active targeting; Amphiphilic block copolymer; Animals; Anti-tumor efficacy; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacokinetics; Biodistribution; Drug Delivery Systems; Galactosylated nanoparticles; Humans; Liver Neoplasms - drug therapy; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Paclitaxel - administration & dosage; Paclitaxel - analogs & derivatives; Paclitaxel - chemistry; Paclitaxel - pharmacokinetics; Tissue Distribution; Tumor Cells, Cultured
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2005.10.027

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.