羧甲基壳聚糖水凝胶的pH敏感性及体外释药性能

目的 研究羧甲基壳聚糖水凝胶（CMCSG）的pH敏感性及在药物控释系统中的应用。方法 采用戊二醛交联法制备不同的CMCSG，经冷冻干燥后测定凝胶在不同pH值溶液中的溶胀动力学特点。观察交联剂用量、羧甲基取代度对凝胶溶胀度的影响及载药凝胶在人工胃液、人工肠液中的释放行为。结果 在pH3．0和5．0的缓冲液中CMCSG均表现较小的溶胀度。随着交联度增大，CMCSG溶胀度减小。低交联度CMCSG的溶胀度在pH7．4缓冲液中显著大于pH1．2缓冲液。羧甲基取代度增大，CMCSG在碱性介质的溶胀度增大。在酸性介质的溶胀度变小；载有牛血清白蛋白（BSA）的凝胶在pH7．4人工肠液中的4h的累积释放度为88％。在pH1．2人工胃液中12h的累积释放度为98％。结论 CMCSG具有pH敏感性，改变羧甲基取代度、交联度可调节CMCSG在不同酸碱介质中的溶胀行为，从而控制药物的释放。

pH Sensitivity of Carboxymethyl Chitosan Hydrogel and Drug Controlled Release in vitro

Objective To investigate the pH sensitivity of carboxymethyl chitosan hydrogel(CMCSG) and its application in drug controlled release system. Methods pH-sensitive hydrogels based on carboxymethyl chitosan(CMCS) were prepared by cross-linking with glutaraldehyde and freeze drying. The effects of the dosage of cross-linking agent and the substitution degree of carboxymethyl of CMCS on the swelling characteristics of CMCSG have been studied. The release behaviors of CMCSG were investigated insimulated gastric and simulated enteric pH conditions respectively. Results With the increasing of the dosage of glutaraldehyde, the swelling degree of CMCSG was decreased. The CMCSG with lower cross-linking at pH 7.4 swelling degree was increased than at pH 1.2 medium, the CMCSG with high cross-linking degree swelled were similarly at pH 7.4 and at pH 1.2 medium. The swelling degree of CMCSG based on high substitution of carboxymethyl in pH 7.4 buffer solution was larger than that in pH 1.2 buffer solution. The cumulated release rate of bovine serum albumin(BSA) entrapped hydrogel in the CMCSG-2 in simulated enteric(pH 7.4) for 4 h was 88%, and in simulated gastric (pH1.2) for 12 h was 98%. Conclusion CMCSG shows pH-sensitivity. Swelling behaviors of CMCSG in alkaline or in acidic solution can be modified by changing the dosage of cross-linking agent or the substitution degree of carboxymethyl of CMCS to control the release rate of drugs loaded in hydrogels.