A thermo-sensitive PLGA-PEG-PLGA hydrogel for sustained release of docetaxel

J Drug Target. 2011 Aug;19(7):516-27. doi: 10.3109/1061186X.2010.519031. Epub 2010 Sep 30.

Abstract

The aim of this study was to investigate the suitability of poly-(d,l-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymer as a matrix material for a sustained-release system for docetaxel (DTX). The copolymers were synthesized by ring-opening polymerization reaction and characterized by (1)H-NMR and gel permeation chromatography. The DTX-loaded formulations were prepared, characterized. And the antitumor efficacy and the pharmacokinetics of DTX-loaded copolymer on A-549 lung tumor-bearing BALB/cA mice were investigated. The results showed that DTX-loaded copolymer highly increased the solubility of DTX by more than 3000-fold. And copolymer concentration as well as drug loading level exerted appreciable influence on the drug release behavior. Further, the pharmacokinetic test showed that DTX-loaded copolymer could be with the sustained-release nature for over 3 weeks, which correlated well with the in vitro release. Additionally, one intratumoral injection of the thermo-sensitive hydrogel containing DTX was comparable to three intravenous injections of DTX injection in inhibiting the tumor growth in A-549 lung tumor-bearing BALB/cA mice with a less toxic manner. PLGA-PEG-PLGA could thus provide a promising alternate locally delivered vehicle for DTX to achieve prolonged exposure having greater efficacy in inhibiting tumor growth with lower toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / blood
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Docetaxel
  • Hydrogels*
  • Inhibitory Concentration 50
  • Lactic Acid*
  • Mice
  • Mice, Inbred BALB C
  • Micelles
  • Neoplasm Transplantation
  • Polyethylene Glycols*
  • Polyglycolic Acid*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Powder Diffraction
  • Rheology
  • Solubility
  • Taxoids / administration & dosage*
  • Taxoids / blood
  • Taxoids / pharmacokinetics
  • X-Ray Diffraction

Substances

  • Antineoplastic Agents, Phytogenic
  • Hydrogels
  • Micelles
  • Taxoids
  • Docetaxel
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Polyethylene Glycols