Improvement of intraperitoneal chemotherapy for rat ovarian cancer using cisplatin-containing microspheres.
Microspheres consisting of L-lactic acid and glycolic acid copolymer containing cisplatin (CDDP-PLGA) were developed to improve the delivery of cisplatin. We evaluated the effects of intraperitoneal administration of cisplatin prepared as CDDP-PLGA in rats with ovarian cancer. The toxicity, platinum distribution, and therapeutic effects of CDDP-PLGA were evaluated as compared with those in the case of cisplatin aqueous solution. The LD50 of CDDP-PLGA was almost four-fold higher than that of cisplatin aqueous solution. CDDP-PLGA released cisplatin slowly and achieved a higher concentration in the peritoneal cavity and in peritoneal tumors for prolonged periods, while the tissue concentration of cisplatin was reduced elsewhere in the body, as compared with the case of cisplatin aqueous solution. The survival of rats with peritoneal carcinomatosis was increased by this delivery system relative to cisplatin aqueous solution. CDDP-PLGA thus allows a higher dose to be given without increasing systemic toxicity, enhancing the therapeutic effect of cisplatin.
Kumagai
S
S
Department of Obstetrics and Gynecology, Kurume University School of Medicine, Fukuoka, Japan.
Sugiyama
T
T
Nishida
T
T
Ushijima
K
K
Yakushiji
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D002626:Chemistry, Pharmaceutical; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D007274:Injections, Intraperitoneal; D019344:Lactic Acid; D008863:Microspheres; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002945:Cisplatin