Low-molecular-weight methylcellulose-based thermo-reversible gel/pluronic micelle combination system for local and sustained docetaxel delivery

Pharm Res. 2012 Feb;29(2):525-34. doi: 10.1007/s11095-011-0581-8. Epub 2011 Sep 9.

Abstract

Purpose: To develop low-molecular-weight methylcellulose (LMw MC)-based gel/Pluronic F127 micelle combination system for local and sustained delivery of docetaxel (DTX).

Methods: LMw MC and Pluronic F127 were used to formulate an injectable thermo-reversible gel/micelle combination system containing DTX. The DTX-loaded combination system was characterized and its therapeutic efficacy evaluated in a subcutaneous tumor model.

Results: Mixtures of LMw MC, AS, and Pluronic F127 formed gel at ~15-40°C depending on AS concentration. The combination system released DTX for >30 days with a biphasic and sustained release pattern, and DTX stability was maintained during release. The combination system significantly enhanced anti-cancer effects of DTX and prolonged survival of the model mouse in comparison with free DTX.

Conclusions: The LMw MC gel/Pluronic F127 micelle combination system constitutes a promising tool for reducing tumor size and eradicating remaining tumor cells before and after surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Delayed-Action Preparations / chemistry*
  • Docetaxel
  • Male
  • Methylcellulose / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Micelles*
  • Neoplasms / drug therapy
  • Poloxamer / chemistry*
  • Taxoids / administration & dosage*
  • Taxoids / pharmacokinetics
  • Taxoids / therapeutic use

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Micelles
  • Taxoids
  • Poloxamer
  • Docetaxel
  • Methylcellulose