Characterization of ring-opening polymerization of genipin and pH-dependent cross-linking reactions between chitosan and genipin

Abstract

In this study, a novel chitosan-based polymeric network was synthesized by crosslinking with a naturally occurring crosslinking agent—genipin. The results showed that the crosslinking reactions were pH-dependent. Under basic conditions, genipin underwent a ring-opening polymerization prior to crosslinking with chitosan. The crosslink bridges consisted of polymerized genipin macromers or oligomers (7 ∼ 88 monomer units). This ring-opening polymerization of genipin was initiated by extracting proton from the hydroxyl groups at C-1 of deoxyloganin aglycone, followed by opening the dihydropyran ring to conduct an aldol condensation. At neutral and acidic conditions, genipin reacted with primary amino groups on chitosan to form heterocyclic amines. The heterocyclic amines were further associated to form crosslinked networks with short chains of dimmer, trimer, and tetramer bridges. An accompanied reaction of nucleophilic substitution of the ester group on genipin by the primary amine group on chitosan would occur in the presence of an acid catalysis. The extent in which chitosan gels crosslinked with genipin was significantly dependent on the crosslinking pH values: 39.9 ± 3.8% at pH 5.0, 96.0 ± 1.9% at pH 7.4, 45.4 ± 1.8% at pH 9.0, and 1.4 ± 1.0% at pH 13.6 (n = 5, p < 0.05). Owing to the different crosslinking extents and different chain lengths of crosslink bridges, the genipin-crosslinked chitosan gels showed significant difference in their swelling capability and their resistance against enzymatic hydrolysis, depending on the pH conditions for crosslinking. These results indicated a direct relationship between the mode of crosslinking reaction, and the swelling and enzymatic hydrolysis properties of the genipin-crosslinked chitosan gels. The ring-opening polymerization of genipin and the pH-dependent crosslinking reactions may provide a novel way for the preparation and exploitation of chitosan-based gels for biomedical applications. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1985–2000, 2005