Antitumor effect of cisplatin incorporated into polylactic acid microcapsules.

Cisplatin containing microcapsules (CDDP-MC) were prepared by encapsulating cisplatin suspended in a dispersing agent in a copolymer (lactic acid) matrix using an in water drying method. Cisplatin release from the microcapsules was controlled by the addition of albumin. The CDDP-MC were relatively stable in storage, and there was only minimal initial release of the cisplatin from the microcapsules. The antitumor effects of this sustained release dosage form of cisplatin were evaluated in vitro and in vivo in mice. Mice were given an intraperitoneal (i.p.) injection of CDDP-MC 24 h after inoculation with tumor cells. The CDDP-MC were effective against Ehrlich ascites tumors and showed reduced acute toxicity compared with standard cisplatin solution. Due to the small initial release of the cisplatin from the microcapsules, however, the antitumor effect of the CDDP-MC was weaker than that of cisplatin solution. Conventional sustained release preparations have been reported to have large particle sizes and demonstrate large releases of cisplatin from microcapsules. They have been considered more effective than cisplatin solution because of the large initial release of cisplatin from the microcapsules and the maintenance of drug levels. The antitumor effect of our slow-release formulation of cisplatin was evaluated by administration of CDDP-MC 1, 4, and 7 days before i.p. implantation of tumor cells. The survival time of the tumor-bearing mice was prolonged in the CDDP-MC group, but not in the group treated with cisplatin solution. By using this modified formulation of cisplatin, the toxicity of the drug can be reduced, and effective concentrations of the drug can be maintained locally for prolonged periods of time.