Release of indomethacin from a novel chitosan microsphere prepared by a naturally occurring crosslinker: Examination of crosslinking and polycation-anionic drug interaction

Novel chitosan microspheres with lower cytotoxicity were fabricated in this study and their drug release characteristics were investigated. Genipin, a naturally occurring crosslinking reagent that has been used in herbal medi cine and in the production of food dye, was used to prepare crosslinked chi tosan microspheres by a water-in-oil dispersion method. The crosslinking me chanism examined by FTIR and C-13-NMR suggests that the crosslinking of chi tosan by genipin leads to the formation of secondary amide and heterocyclic amino linkage. The polycation-anionic drug interaction between chitosan an d indomethacin was pH dependent and could affect the dissolution property o f indomethacin. By examination of the release profiles of tile crosslinked chitosan microsphere, it was found that the release of indomethacin from th e microsphere was sustainable and influenced by factors such as crosslinkin g of microsphere and chitosan-indomethacin interaction, thus establishing c rosslinked chitosan microsphere as a very promising polymeric carrier for d rug release. (C) 2001 John Wiley & Sons, Inc.