Properties of Water-Insoluble Mitomycin C-Albumin Conjugate as a Sustained Release Drug Delivery System in Mice Inoculated with Sarcoma 180

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In order to improve the deposition of mitomycin C (MMC) in the administered site, water-insoluble mitomycin C-albumin conjugate (MMC-G-BSA) was prepared. MMC was covalently attached to the glutarylated bovine serum albumin (G-BSA) in the presence of 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide 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 suspended in a phosphate buffer (pH 7.4,37℃) with a half-life of 155.3 h. In the same buffer system containing α-chymotrypsin, MMC-G-BSA was dissolved perfectly within 24h due to enzymatic degradation, and the liberation of MMC from the conjugate was significantly accelerated (t_<1/2>=24.5 h). After intraperitoneal injection in mice, most of the MMC-G-BSA was retained in the abdominal cavity. Furthermore, the survival time of mice inoculated with Sarcoma 180 was significantly increased by the intraperitoneal injection of MMC-G-BSA. These findings suggest that MMC-G-BSA is a biodegradable macromolecular hybrid which acts as a sustained release delivery system of MMC.
社団法人日本薬学会の論文
1995-12-15