pH-Sensitive swelling of polyelectrolyte complex gels prepared from natural polymers and its application to controlled release systems for oral drug delivery

天然聚合物制备的聚电解质复合凝胶的 pH 敏感溶胀及其在口服给药控释系统中的应用

基本信息

批准号：
09650880
负责人：
SAKIYAMA Takaharu
金额：
$ 2.18万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Polyelectrolyte complex gel prepared from a basic polysaccharide chitosan together with an acidic polysaceharide shows pH-sensitive swelling. In this study, the pH- sensitive swelling behavior and its applicability to pH-controlled release systems for drugs were investigated mainly on complex gels prepared from dextran sulfate and chitosan : The swelling behaviors of the complex gels were analyzed on the basis of Donnan equilibrium, It was shown that dissociation of protonated amino groups was a key step for the prominent volume change observed when the complex gel swelled or shrank. To study the courses of drug release under various conditions from a complex gel with excess amino group, dextran, bovine serum albumin (BSA), lactoferrin, and Indomethacin were used as model drugs. The complex gel with excess amino group shrank at around pH 7. The apparent diffusion coefficient of dextran inside the gel increased by 3 to 10 times due to squeezing effect caused by shrinking of the complex gel. Release of BSA from the complex gel was accelerated at pHs above 6 where the complex gel shrank. Sustained release of lactoferrin was observed at pH 8.8, above the isoelectric point of lactoferrin. These results indicate that the electrostatic interaction between the gel and model drugs affects the releasing behavior as well as the squeezing effect by shrinking of the complex gel. Sustained release of Indomethacin from the complex gel was observed at pHs above 6. Thus the complex gel would be useful as a material for p H-controlled release of drags.

由碱性多糖壳聚糖和酸性多糖制备的聚电解质复合凝胶表现出pH敏感性溶胀。本研究主要针对硫酸葡聚糖和壳聚糖制备的复合凝胶的pH敏感溶胀行为及其在药物pH控释系统中的适用性进行了研究：基于Donnan平衡分析了复合凝胶的溶胀行为，结果表明，质子化氨基的解离是复合凝胶膨胀或收缩时观察到的显着体积变化的关键步骤。为了研究具有过量氨基的复合凝胶在不同条件下的药物释放过程，以右旋糖酐、牛血清白蛋白(BSA)、乳铁蛋白和吲哚美辛作为模型药物。含有过量氨基的复合凝胶在pH 7附近发生收缩。由于复合凝胶收缩产生的挤压效应，凝胶内葡聚糖的表观扩散系数增加了3～10倍。当 pH 值高于 6 时，复合凝胶会收缩，BSA 从复合凝胶中的释放会加速。在 pH 8.8（高于乳铁蛋白的等电点）时观察到乳铁蛋白的持续释放。这些结果表明，凝胶和模型药物之间的静电相互作用影响释放行为以及复杂凝胶收缩的挤压效应。在pH值高于6时观察到吲哚美辛从复合凝胶中持续释放。因此，复合凝胶可用作药物的pH控制释放的材料。