Fluorouracil-Polyglycolic Acid Composite as an Intraperitoneal Chemotherapeutic Agent

ABSTRACT

BACKGROUND: There is a great need for a new drug delivery system that provides higher sustained exposure of the anticancer drug to the peritoneal surface or lymphatics with a lower systemic toxicity. Intraperitoneal chemotherapy will be an effective therapeutic strategy for disseminated microscopic disease and small miliary nodules remaining on the peritoneal surface after surgery. The auther has made a fluorouracil-polyglycolic acid composite disk (Fu-PGA disk) for a more effective intraperitoneal chemotherapeutic agent. METHODS: The Fu-PGA disk(s) was (were) inserted in the peritoneal cavity of a rat, and a pharmacokinetic study was performed to measure fluorouracil concentration in the peritoneal fluid, plasma, liver, kidney and heart tissue at day 1, day 3, day 7, and day 14 after administration of the agent. The myelosuppressive action of this composite was also determined following its administration. RESULTS: After administration of the Fu-PGA disks, the 5-Fu concentration of the peritoneal fluid of the rat was much higher than that of the plasma. Also, the 5-Fu concentrations of the liver, kidney and heart tissue were very low. The numbers of white cells and platelets decreased after administration of the Fu-PGA disks, but they were almost recovered to normal range at day 14th. Only focal necrosis around the central veins of the liver and minimal vacuolar degeneration in the proximal tubules of the kidney were observed microscopically. CONCLUSION: This animal study suggests that the Fu-PGA composite can be used as a new biodegradable drug delivery system for releasing the drug in a controlled manner with the peritoneum as its target. This Fu-PGA device may overcome some of the disadvantages of conventional anticancer chemotherapy and improve the efficacy of intraperitoneal chemotherapy.