Mitomycin C carrying microspheres as a novel method of drug delivery.

Abstract

Biodegradable albumin microspheres containing about 5% mitomycin C (MMC) were prepared in an average diameter of 45 +/- 8 microns by heat denaturation in oil at 120 degrees C and/or cross-linking with glutaraldehyde. These MMC microspheres released, in vitro, about 20% of the contained MMC for over 3 days, and they were intra-arterially infused into albino rabbits and Wistar rats, as a preclinical model of intra-arterial infusion treatment for patients with inoperable hepatic tumor. We infused these microspheres into the femoral artery of rabbits with a VX-2 tumor implanted into the flank of the hindleg. High levels of MMC were maintained for several hours in the tumor and the entrapped MMC microspheres were detected within arterioles in the VX-2 tumors. The growth of VX-2 tumor was inhibited considerably, compared to findings in the control rabbits given conventional MMC. In the next studies, MMC microspheres were infused into the rat hepatic artery, and the levels of MMC in the hepatic vein blood were maintained at much the same concentration for over 2 hours after the infusion, in marked contrast to rapid decreases in the conventional MMC. Histologic findings revealed that MMC micro-spheres were entrapped within the hepatic arterioles for over 2 weeks and released biologically active MMC into the neighboring tissues for prolonged periods of time.