The antitumor effect of novel docetaxel-loaded thermosensitive micelles

Eur J Pharm Biopharm. 2008 Jun;69(2):527-34. doi: 10.1016/j.ejpb.2008.01.015. Epub 2008 Jan 26.

Abstract

To further evaluate the novel docetaxel-loaded micelle based on the biodegradable thermosensitive copolymer poly(N-isopropylacrylamide-co-acrylamide)-b-poly(dl-lactide) that we had synthesized before, in this paper, we studied its in vitro cytotoxicity in three different tumor cell lines by standard MTT assays using different tumor cell lines, followed by studies of acute toxicity and the tumor distribution studies which were conducted in Kunming mice. Meanwhile, the in vivo antitumor efficacy as well as toxicity of the micelle was evaluated in C57BL/6 mice. According to our findings, the in vitro cytotoxicity of docetaxel-loaded micelles was lower than that of the conventional docetaxel formulation at 37 degrees C, while hyperthermia greatly enhanced the efficacy of drug-loaded micelles. The acute toxicity study showed reduced toxicity of docetaxel-loaded micelle compared to that of conventional docetaxel formulation. Moreover, docetaxel-loaded micelle enabled a prominent higher docetaxel concentration in tumor than conventional docetaxel formulation. Furthermore, a significantly higher antitumor efficacy was observed in mice treated with docetaxel-loaded micelles accompanied by hyperthermia; docetaxel-loaded micelles also caused less body weight loss of mice. This study demonstrates an increased antitumor efficacy and reduced toxicity of the novel docetaxel-loaded micelle and indicates its prospect of clinical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Carcinoma, Lewis Lung / drug therapy
  • Cell Survival / drug effects
  • Docetaxel
  • Lethal Dose 50
  • Lung Neoplasms / drug therapy
  • Mice
  • Mice, Inbred C57BL
  • Micelles
  • Neoplasm Transplantation
  • Sarcoma 180 / drug therapy
  • Taxoids / administration & dosage*
  • Taxoids / pharmacokinetics
  • Taxoids / pharmacology*
  • Temperature
  • Tissue Distribution

Substances

  • Antineoplastic Agents, Phytogenic
  • Micelles
  • Taxoids
  • Docetaxel