5-FU-hydrogel inhibits colorectal peritoneal carcinomatosis and tumor growth in mice

BMC Cancer. 2010 Aug 2:10:402. doi: 10.1186/1471-2407-10-402.

Abstract

Background: Colorectal peritoneal carcinomatosis (CRPC) is a common form of systemic metastasis of intra-abdominal cancers. Intraperitoneal chemotherapy is a preferable option for colorectal cancer. Here we reported that a new system, 5-FU-loaded hydrogel system, can improve the therapeutic effects of intraperitoneal chemotherapy.

Methods: A biodegradable PEG-PCL-PEG (PECE) triblock copolymer was successfully synthesized. The biodegradable and temperature sensitive hydrogel was developed to load 5-FU. Methylene blue-loaded hydrogel were also developed for visible observation of the drug release. The effects and toxicity of the 5-FU-hydrogel system were evaluated in a murine CRPC model.

Results: The hydrogel system is an injectable flowing solution at ambient temperature and forms a non-flowing gel depot at physiological temperature. 5-FU-hydrogel was subsequently injected into abdominal cavity in mice with CT26 cancer cells peritoneal dissemination. The results showed that the hydrogel delivery system prolonged the release of methylene blue; the 5-FU-hydrogel significantly inhibited the peritoneal dissemination and growth of CT26 cells. Furthermore, intraperitoneal administration of the 5-FU-hydrogel was well tolerated and showed less hematologic toxicity.

Conclusions: Our data indicate that the 5-FU-hydrogel system can be considered as a new strategy for peritoneal carcinomatosis, and the hydrogel may provide a potential delivery system to load different chemotherapeutic drugs for peritoneal carcinomatosis of cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology*
  • Drug Delivery Systems*
  • Female
  • Fluorouracil / therapeutic use*
  • Humans
  • Hydrogels*
  • Mice
  • Mice, Inbred BALB C
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / secondary
  • Polyesters / chemistry
  • Polyethylene Glycols / chemistry
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Polymers / pharmacology

Substances

  • Antimetabolites, Antineoplastic
  • Hydrogels
  • Polyesters
  • Polymers
  • poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol)
  • Polyethylene Glycols
  • Fluorouracil