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 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 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 accelerated (t1/2 = 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.
Tanaka
T
T
Department of Biopharmaceutics, Fukuyama University, Japan.
Kaneo
Y
Y
Miyashita
M
M
Shiramoto
S
S
D000418:Albumins / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D051379:Mice; D016685:Mitomycin / Q000008:administration & dosage* / Q000737:chemistry; D012510:Sarcoma 180 / Q000188:drug therapy*
D000418:Albumins; D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D016685:Mitomycin