PROPERTIES OF WATER-INSOLUBLE MITOMYCIN C-ALBUMIN CONJUGATE AS A SUSTAINED-RELEASE DRUG-DELIVERY SYSTEM IN MICE INOCULATED WITH SARCOMA-180

In order to improve the deposition of mitomycin C (MMC) in the adminis tered site, water-insoluble mitomycin C-albumin conjugate (MMC-G-BSA) was prepared. MMC was covalently attached to the glutarylated bovine s erum albumin (G-BSA) in the presence of 1-ethyl-3-(3-dimethyl-aminopro pyl)carboiimide hydrochloride (EDC) to give MMC-G-BSA. The MMC content of the conjugate (16.3% (w/w)) was higher than that of water-soluble mitomycin C-albumin conjugates. MMC was liberated from MMC-G-BSA suspe nded in a phosphate buffer (pH 7.4, 37 degrees C) with a half-life of 155.3 h. In the same buffer system containing alpha-chymotrypsin, MMC- G-BSA was dissolved perfectly within 24 h due to enzymatic degradation , and the liberation of MMC from the conjugate was significantly accel erated (t(1/2) = 24.5 h). After intraperitoneal injection in mice, mos t of the MMC-G-BSA was retained in the abdominal cavity. Furthermore, the survival time of mice inoculated with Sarcoma 180 was significantl y increased by the intraperitoneal injection of MMC-G-BSA. These findi ngs suggest that MMC-G-BSA is a biodegradable macromolecular hybrid wh ich acts as a sustained release delivery system of MMC.