DESIGN AND TESTING OF A NEW CISPLATIN FORM USING A BASE MATERIAL BY COMBINING POLY-D,L-LACTIC ACID AND POLYETHYLENE-GLYCOL ACID AGAINST PERITONEAL METASTASIS

Microspheres containing cisplatin (CDDP) embedded in poly-d,l-lactic a cid (PLA) and polyethylene glycol acid (CDDP-PPMS) were developed to i mprove treatment of malignant effusions. In vitro studies demonstrated that CDDP was released continuously for more than 4 weeks from CDDP-P PMS without initial burst. CDDP-PPMS was compared with CDDP aqueous so lution (CDDP-SOL) by i.p. administration in rats for 1) tissue distrib ution, 2) toxicity and 3) therapeutic effects against Yoshida sarcoma. We found that the CDDP concentration in the omentum was maintained at a higher level than in the CDDP-SOL group, while the particles of CDD P-PPMS were observed in the stomata of the omentum by electron microsc opy. Concentrations of CDDP in the lung, liver, kidney and blood were lower in the CDDP-PPMS group than in the CDDP-SOL group. All rats give n CDDP-PPMS containing less than or equal to 28 mg/kg were alive, wher eas in the CDDP-SOL group, all rats given greater than or equal to 16 mg/kg died from side effects. The LD50 of CDDB-PPMS and CDDP-SOL were 32.8 and 14.8 mg/kg, respectively. The survival of rats with peritonea l metastasis was better in the CDDP-PPMS group than in the CDDP-SOL gr oup. (C) 1998 Wiley-Liss, Inc.