Properties of water-insoluble mitomycin C-albumin conjugate as a sustained release drug delivery system in mice inoculated with Sarcoma 180.

Abstract

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.

• Authors: T Tanaka, Y Kaneo, M Miyashita, S Shiramoto
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 18 Issue 12 Pg. 1724-8 (Dec 1995) ISSN: 0918-6158 [Print] Japan
• PMID: 8787796 (Publication Type: Journal Article)

Chemical References

• Albumins
• Antibiotics, Antineoplastic
• Delayed-Action Preparations
• Mitomycin

Topics

• Albumins (administration & dosage, chemistry)
• Animals
• Antibiotics, Antineoplastic (administration & dosage)
• Delayed-Action Preparations
• Mice
• Mitomycin (administration & dosage, chemistry)
• Sarcoma 180 (drug therapy)