Synthesis and characterization of biodegradable hydrogels based on chitosan derivatives, and their applications for drug delivery system

Abstract

In this study, two kinds of chitosan derivatives were synthesized and then used for the preparation of biodegradable stimuli-sensitive hydrogels by radical polymerization with a monomer. One is maleoyl chitosan(MC) prepared from the reaction of chitosan with maleic anhydride in the formamide solution. The other is N,O-methacryloyl chitosan(NOMAC) which was synthesized by the reaction of chitosan with methacrylic anhydride at pH 6.0 in aqueous solution. MC had not only vinyl groups but also carboxylate groups so that this compound dissolved in basic solution while precipitated in acidic solution. Moreover, MC showed higher biodegradability than chitosan with lysozyme. In the case of NOMACs with various degree of substitutions, vinyl groups and free amine were introduced to this derivatives. Therefore, these two kinds of chitosan derivatives were used as pH-sensitive macromers which were able to crosslink to a monomer such as N-isopropylacrylamide (NIPAAm) or acrylic acid(AAc) by radical polymerization. First of all, pH/temperature-sensitive hydrogels composed of MC and NIPAAm were synthesized with a formulation of disc type and microsphere and then characterized with respect to the change of the phase volume transition temperature, biodegradability, and drug release depending on pH. The hydrogels swelled in high pHs due to the ionization of the carboxylate groups of MC but deswelled in low pHs because of the protonation of carboxylate groups. The hydrogels also swelled below the around 32 ？ due to the hydrophilicity of PNIPAAm components while deswelled above the temperature resulting from the change to hydrophobicity of PNIPAAm components. Especially, the hydrogels still exhibited phase volume transition temperature significantly at the high pHs even though a large amount of carboxylate groups of MC were introduced to the hydrogels. This is because carboxylate groups existed in the segment different from PNIPAAm segment like the PNIPAAm grafted to polyacrylic a...