Drug release from chitosan-alginate complex beads reinforced by a naturally occurring cross-linking agent
2002
Mi, F.L. | Sung, H.W. | Shyu, S.S.
Cross-linking reinforced chitosan-alginate complex beads were prepared by dropping chitosan droplets into alginate-cross-linker co-existing gelling solution. A novel, naturally occurring material -- genipin was used as the cross-linking agent. Genipin and its related iridoid compounds, extracted from the Gardenia fruits, have been used in the traditional Chinese medicine for the treatments of jaundice and various inflammatory and hepatic diseases. The gelation of chitosan droplets in alginate-genipin mixed solution depends on both controlling factors: chitosan-alginate polyelectrolyte complex and chitosan cross-linked by genipin. The reaction of chitosan-alginate complex dominates the formation of skin layer on the surface of beads, but cross-linking of chitosan by genipin dominates the curing of inner core of beads. The swelling ratio of the cross-linking reinforced chitosan-alginate complex bead decreases as the pH or concentration of alginate in the gelling solution was decreased. The protonation of amine group of chitosan by hydrogen ions from acid or the shield of charge of ammonium group of chitosan by Cl- ions result in the decrease of cross-linking density due to the inhibition of nucleophilic attack on the dihydropyran ring of genipin. Contrary to the swelling properties, the rate of indomethacin releasing out of the chitosan-alginate complex beads increases with the decrease in pH or concentration of alginate in the gelling solution due to the decreased cross-linking density of the beads. The cytotoxic examination suggested that the chitosan-alginate beads cross-linked by genipin had a good cellular compatibility.
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