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

由碱性多糖壳聚糖和酸性多糖壳聚糖制备的聚电解质复合物凝胶显示pH敏感性溶胀。本文主要研究了硫酸葡聚糖-壳聚糖复合凝胶的pH敏感性溶胀行为及其在药物pH控制释放系统中的应用。根据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溶胀或收缩时体积显著变化的关键步骤。为了研究在各种条件下从具有过量氨基的复合凝胶中释放药物的过程，使用葡聚糖、牛血清白蛋白（BSA）、乳铁蛋白和吲哚美辛作为模型药物。具有过量氨基的复合物凝胶在pH 7左右收缩。由于复合凝胶收缩产生的挤压效应，葡聚糖在凝胶内的表观扩散系数增加了3 ~ 10倍。BSA从复合物凝胶中的释放在pH高于6时加速，此时复合物凝胶收缩。在pH 8.8下观察到乳铁蛋白的持续释放，高于乳铁蛋白的等电点。这些结果表明，凝胶与模型药物之间的静电相互作用影响的释放行为，以及通过收缩的复合凝胶的挤压效应。吲哚美辛从复合物凝胶中的持续释放在pH高于6时观察到。因此，该复合物凝胶可用作药物的pH控制释放材料。

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.