Preparation and in vitro properties of N-succinylchitosan- or carboxymethylchitin-mitomycin C conjugate microparticles with specified size.

The preparation of cross-linked conjugate microparticles of N-succinyl-chitosan (Suc) or 6-O-carboxymethylchitin (CM) with mitomycin C (MMC), which showed an adequate si-e for liver targeting (0.2-3 microm), was attempted by a combination of water-soluble carbodiimide (EDC) coupling and emulsification technique. As for Suc, microparticles with a diameter less than a few micrometers could be obtained easily, while the preparation of CM microparticles (CM-MPs) of the same diameter was not necessarily easy. First, preparation conditions were compared for CM-MPs, and some conditions gave CM-MPs with a diameter less than a few micrometers. As to CM-MMC conjugate microparticles, the method by addition of EDC after emulsification using CM with low molecular weight (CML) gave more appropriate microparticles with a mean diameter of 0.97microm (CM1-MP-MMC). Suc-MMC conjugate microparticles adequate for liver targeting could be produced by the addition of EDC both before and after emulsification, especially, the conjugate microparticles with a mean diameter of 0.45 microm (Suc-MP-MMC) were derived by the addition of EDC before emulsification. Suc-MP-MMC exhibited a higher drug content than CML-MP-MMC. CML-MP-MMC and Suc-MP-MMC exhibited 50% drug release times of 2.87h and 42.1 h, respectively.