A new anticancer drug delivery system for the management of carcinomatous peritonitis.
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 microns 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.
Yamada
T
T
First Department of Surgery, Kanazawa University School of Medicine, Japan.
Sakatoku
M
M
Ohhira
M
M
Watanabe
Y
Y
Iwa
T
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004337:Drug Carriers; D004906:Erythrocyte Count / Q000187:drug effects; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D007958:Leukocyte Count / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008863:Microspheres; D010538:Peritonitis / Q000150:complications / Q000188:drug therapy*; D010976:Platelet Count / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D004337:Drug Carriers; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005472:Fluorouracil