Galactose-decorated cross-linked biodegradable poly(ethylene glycol)-b-poly(ε-caprolactone) block copolymer micelles for enhanced hepatoma-targeting delivery of paclitaxel

Biomacromolecules. 2011 Aug 8;12(8):3047-55. doi: 10.1021/bm2006856. Epub 2011 Jul 14.

Abstract

The inferior in vivo stability of micellar drugs has been a prime challenge for their application in targeted drug delivery. Here we report on novel galactose-decorated covalently cross-linked biodegradable micelles based on photo-cross-linkable poly(ethylene glycol)-b-poly(acryloyl carbonate)-b-poly(ε-caprolactone) (PEG-PAC-PCL) and galactose-conjugated PEG-PCL (Gal-PEG-PCL) copolymers for enhanced hepatoma-targeting delivery of paclitaxel (PTX). The molecular weight of PEG in Gal-PEG-PCL was higher than that in PEG-PAC-PCL, thereby fully exposing Gal ligands at the micellar surface. These micelles, either with or without loading of PTX, were readily cross-linked by UV irradiation to afford micelles with small sizes (ca. 79-94 nm) and enhanced stability. The in vitro release studies confirmed that drug release from cross-linked micelles was significantly inhibited. Interestingly, MTT assays showed that Gal-decorated PTX-loaded cross-linked micelles retained a high antitumor activity in HepG2 cells, which was much more effective than PTX-loaded cross-linked micelles without Gal ligands and comparable to Gal-decorated PTX-loaded non-cross-linked micelles. Remarkably, the preliminary in vivo antitumor efficacy studies in SMMC-7721 tumor (human hepatoma)-bearing nude mice revealed that Gal-decorated PTX-loaded cross-linked micelles inhibited the growth of the human hepatoma more effectively than PTX-loaded cross-linked micelles as well as Gal-decorated PTX-loaded non-cross-linked micelles. These results indicate that Gal-decorated cross-linked PEG-PCL micelles have great potential in liver tumor-targeted chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Biocompatible Materials*
  • Drug Carriers
  • Ethylene Glycols / chemistry*
  • Galactose / chemistry*
  • Humans
  • Liver Neoplasms, Experimental / drug therapy*
  • Magnetic Resonance Spectroscopy
  • Mice
  • Micelles*
  • Paclitaxel / administration & dosage*
  • Paclitaxel / therapeutic use
  • Polyesters / chemistry*

Substances

  • Antineoplastic Agents, Phytogenic
  • Biocompatible Materials
  • Drug Carriers
  • Ethylene Glycols
  • Micelles
  • Polyesters
  • poly(epsilon-caprolactone)-b-poly(ethylene glycol)
  • Paclitaxel
  • Galactose