Synthesis and drug-release characteristics of the conjugates of mitomycin C with N-succinyl-chitosan and carboxymethyl-chitin.

By condensation of mitomycin C (MMC) with N-succinyl-chitosan (Suc-chitosan) and carboxymethyl-chitin (CM-chitin) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, Suc-chitosan-MMC conjugate (Suc-chitosan-MMC) and CM-chitin-MMC conjugate (CM-chitin-MMC) were prepared, respectively. The reaction conditions for 45 min at pH 5 and for 2 h at pH 5 were selected as the most appropriate for the preparations of Suc-chitosan-MMC and CM-chitin-MMC, respectively. Suc-chitosan-MMC was obtained as a water-insoluble product, while CM-chitin-MMC was partially water-soluble. When the ratio of MMC to the polymer supports changed in the conjugation reaction, the conjugates with 33% (w/w) and 23% (w/w) MMC contents were obtained as those most highly drug-loaded for Suc-chitosan-MMC and CM-chitin-MMC, respectively. At pH 7.4 at 37 degrees C, Suc-chitosan-MMC regenerated MMC very slowly, while the release of MMC from CM-chitin-MMC was relatively fast. Each drug release followed very nearly pseudo-first order kinetics, in which the apparent drug release rate constants (k(apps)) of Suc-chitosan-MMC and CM-chitin-MMC were 3.9 x 10(-3) and 1.1 x 10(-1) (h-1), respectively.