Docetaxel-loaded thermoresponsive conjugated linoleic acid-incorporated poloxamer hydrogel for the suppression of peritoneal metastasis of gastric cancer

Biomaterials. 2013 Jan;34(4):1433-41. doi: 10.1016/j.biomaterials.2012.10.077. Epub 2012 Nov 19.

Abstract

We evaluated the potential of a thermoresponsive hydrogel consisting of conjugated linoleic acid-coupled Pluronic F-127 (Plu-CLA) as a controlled release, intraperitoneal delivery system for docetaxel with the aim of treating peritoneal dissemination of gastric cancer. Previously, we established a peritoneal metastasis model that involves the injection of BALB/c mice with TMK1 human gastric cancer cells. One week after the TMK1 cells were injected, the mice were injected intraperitoneally with docetaxel alone or docetaxel-loaded Plu-CLA. Tumor progression and response to therapy were monitored by micro-positron emission tomography. The total number of peritoneal tumors and the ascites volume were also measured. Compared with docetaxel alone, the combination of docetaxel and Plu-CLA (docetaxel-Plu-CLA) significantly and synergistically reduced tumor cell survival. Docetaxel-Plu-CLA showed excellent anti-tumor activity, inducing apoptosis more potently than docetaxel alone. Docetaxel-Plu-CLA also significantly reduced the number of peritoneal metastatic nodules and increased survival in the peritoneal gastric cancer xenograft model. Our results show that intraperitoneal administration of docetaxel-Plu-CLA synergistically inhibits peritoneal metastasis and prolongs survival in a peritoneal gastric cancer model. Therefore, Plu-CLA is a potential intraperitoneal-route carrier for hydrophobic docetaxel for the effective treatment of peritoneal metastatic gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry
  • Docetaxel
  • Hot Temperature
  • Hydrogels / chemistry
  • Linoleic Acid / chemistry
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanocapsules / administration & dosage*
  • Nanocapsules / chemistry*
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / pathology
  • Peritoneal Neoplasms / secondary*
  • Poloxamer / chemistry*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Taxoids / administration & dosage*
  • Taxoids / chemistry
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Hydrogels
  • Nanocapsules
  • Taxoids
  • Poloxamer
  • Docetaxel
  • Linoleic Acid