Preparation and In Vitro Properties of N-Succinylchitosan– or Carboxymethylchitin–Mitomycin C Conjugate Microparticles with Specified Size

Abstract

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 size for liver targeting (0.2–3 μm), 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 (CM_L) gave more appropriate microparticles with a mean diameter of 0.97 μm (CM_L-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 μm (Suc-MP-MMC) were derived by the addition of EDC before emulsification. Suc-MP-MMC exhibited a higher drug content than CM_L-MP-MMC. CM_L-MP-MMC and Suc-MP-MMC exhibited 50% drug release times of 2.87 h and 42.1 h, respectively.

• 6-O-Carboxymethylchitin
• Cross-linked conjugate microparticles
• Mitomycin C
• N-Succinyl-chitosan