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

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.

• Authors: Woo Kyun Bae, Myong Suk Park, Ji Hee Lee, Jun Eul Hwang, Hyun Jeong Shim, Sang Hee Cho, Dae-Eun Kim, Hyang Mi Ko, Chong-Su Cho, In-Kyu Park, Ik-Joo Chung
• Journal: Biomaterials (Biomaterials) Vol. 34 Issue 4 Pg. 1433-41 (Jan 2013) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 23174142 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

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