Effects of intra-arterially infused biodegradable microspheres containing mitomycin C

We prepared biodegradable microspheres containing about 5% mitomycin C (MMC) and of 45 +/- 8 microns in diameter. These preparations were infused into the rat hepatic artery as a preclinical model of intra-arterial infusion treatment for patients with inoperable hepatic tumor. The leaked MMC levels in the hepatic vein decreased below the assay limitation 2 hours after conventional MMC injection, whereas in the case of MMC microsphere the leaked drug levels were maintained at almost the same concentration for over 2 hours after infusion. The entrapped period of MMC microspheres within the hepatic artery was at least 2 weeks, and the necrobiotic foci due to antitumor effects of the condensed MMC released from the microspheres were observed in the area fed by these entrapped arterioles. This phenomenon was never observed in the case of conventional MMC and placebo microspheres. Intra-arterial infusion of MMC microspheres may be a promising clinical treatment for patients with malignant hepatic tumor.