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To develop a new drug delivery system for the treatment of carcinomatous peritonitis, we constructed 5-fluorouracil poly L-microcapsules (5Fu-mc) by the organic phase separation technique and examined their drug-releasing capacities and anticancer effects. The microcapsules consisted of in vitro dissolvable polymolecular poly L-lactic acid and 5-fluorouracil (5Fu). The 5Fu-mc was about 200 μm in diameter and had a 5Fu content of about 40% (weight/weight). 5Fu-release time from the microcapsules was about 50 hours in vitro and about 48 hours in vivo. After the release of the 5Fu, the poly L-lactic acid was metabolized very slowly in the peritoneal cavity. The 5Fu-mc caused fewer side effects than the equivalent dose of a 5Fu solution. In addition, macroscopic and microscopic examinations of various abdominal organs revealed no toxic effects from the microcapsules. After administration of 5Fu-mc into the abdominal cavity of rats with AH-130 carcinomatous peritonitis, the 5Fu concentration remained at a high level for an extended period in the ascites but fell rapidly to low levels in the plasma. In conclusion, the present studies indicated that the 5Fu-mc were much more effective in prolonging the life of tumor-bearing hosts while producing less systemic side effects than a 5Fu solution.
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Accepted: June 25, 1990
© 1991 Published by Elsevier Inc.