In vivo suppressive effects of copoly(glycolic/L-lactic acid) microspheres containing CDDP on murine tumor cells

Abstract Microspheres composed of a L-lactic acid/glycolic acid copolymer and containing cisplatin (CDDP) (CDDP-MS) were prepared for the sustained release of CDDP with the solvent evaporation method using oil-in-oil emulsion. CDDP was released in vitro from the CDDP-MS over 20 days following about 25% release during the first day. The CDDP-MS implanted into the femoral muscles of rats released CDDP around the implantation site over a few months. The weight loss of mice given the intraperitoneal (ip) injection of CDDP-MS was small compared with that of free CDDP, indicating a reduction in the systemic toxicity of CDDP by its microsphere incorporation. This led to an enhanced suppressive effect of CDDP on the growth of murine tumor cells. The ip injection of CDDP-MS prolonged the survival period of mice with ascitic P815 tumor cells to a significant extent compared with that of free CDDP. In addition, the concentration of blood urea nitrogen was low in the tumor-bearing mice receiving the CDDP-MS injection compared with free CDDP injection, although the CDDP dose was 4 times or more higher than its LD 50 value. It was concluded that the CDDP-MS is a promising drug-carrier system which enhances the antitumor effect of CDDP and reduces its systemic toxicity.