Preparation and Drug Release Characteristics of the Conjugates of Mitomycin C with Glycol-chitosan and JV-Succinyl-chitosan

摘要

Mitomycin C (MMC) was covalently attached to glycol-chitosan (Gly-chitosan) and iV-succinyl-chitosan (JV-Suc-chitosan) through a spacer of the glutaryl group, and each conjugate was obtained as a water-soluble product. Stability of la-(4-carboxybutyryl)-MMC (Glu-MMC) in vitro was investigated by incubation in 1/15m phosphate buffers of pH 5, 6, 7.4, 8 and 9 at 37 °C. The release rate of MMC from Glu-MMC was very slow at neutral pH, gradual at basic pH and relatively fast at acidic pH, but the quick decomposition of MMC proceeded simultaneously at acidic pH. Release of MMC from the conjugates in vitro was investigated by incubation in 1/15 m phosphate buffers of pH 5,7.4 and 9 at 37 °C. The release rate of MMC from the conjugates was slight at acidic pH, accelerated at basic pH, and was gradual at pi I 7.4. In a plasma-buffer (pH 7.4) mixture (1:1, v/v), the release rate of MMC from the conjugates was rather similar to that in only the buffer (pH 7.4).