Synthesis and characterization of the paclitaxel/MPEG-PLA block copolymer conjugate

Biomaterials. 2005 May;26(14):2121-8. doi: 10.1016/j.biomaterials.2004.06.024.

Abstract

A paclitaxel/MPEG-PLA block copolymer conjugate was prepared in three steps: (1) hydroxyl-terminated diblock copolymer of monomethoxy-poly(ethylene glycol)-b-poly(lactide) (MPEG-PLA) was synthesized by ring-opening polymerization of L-lactide using MPEG as a maroinitiator; (2) it was converted to carboxyl-terminated MPEG-PLA by reacting with mono-t-butyl ester of diglycolic acid and subsequent deprotecting the t-butyl group with TFA; (3) the latter was reacted with paclitaxel in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. Structures of the polymers synthesized were confirmed by (1)H NMR, and their molecular weights were determined by gel permeation chromatography. The antitumor activity of the conjugate against human liver cancer H7402 cells was evaluated by MTT method. The results showed that paclitaxel can be released from the conjugate without losing cytotoxicity.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Biocompatible Materials / chemistry
  • Cell Line, Tumor
  • Delayed-Action Preparations / administration & dosage*
  • Delayed-Action Preparations / chemistry*
  • Diffusion
  • Humans
  • Liver Neoplasms / drug therapy*
  • Materials Testing
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry*
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biocompatible Materials
  • Delayed-Action Preparations
  • Polyesters
  • methoxy poly(ethylene glycol)-poly(lactide)
  • Polyethylene Glycols
  • Paclitaxel