Conjugate of mitomycin C with N-succinyl-chitosan: In vitro drug release properties, toxicity and antitumor activity

Macromolecular conjugates between N-succinyl-chitosan (Suc-chitosan) and mitomycin C (MMC), referred to as Suc-chitosan-MMC, were prepared. Conjugates with different drug contents were investigated with respect to in vitro drug regeneration rates. Suc-chitosan, MMC and Suc-chitosan-MMC were evaluated for acute toxicity using normal mice, and antitumor activity was investigated using mice bearing P388 leukemia. Some treatment schedules were also studied for the conjugate. The percent rates of MMC release were similar among the conjugates with different drug contents. Suc-chitosan was not toxic on intraperitoneal administration at 2 g/kg. The LD50 of the conjugate was about 3-times of that of MMC. Suc-chitosan alone exhibited no antitumor activity. The conjugate showed a higher maximum ILS value than MMC. A mixture of MMC and Suc-chitosan-MMC displayed a much higher ILS value than the conjugate alone at equivalent dose (5 mg eq MMC/kg).