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制备的聚电解质复合凝胶具有ph敏感性膨胀。本研究主要考察了硫酸葡聚糖和壳聚糖复合凝胶的pH敏感性溶胀行为及其在药物pH控释体系中的应用，并根据Donnan平衡分析了复合凝胶的溶胀行为。结果表明，当复合凝胶膨胀或收缩时，质子化氨基的解离是其体积变化显著的关键步骤。以葡聚糖、牛血清白蛋白（BSA）、乳铁蛋白和吲哚美辛为模型药物，研究不同条件下过量氨基复合凝胶的释药过程。氨基酸过量的复合物凝胶在pH 7左右收缩。凝胶内葡聚糖的表观扩散系数由于复合凝胶收缩引起的挤压作用提高了3 ~ 10倍。当ph值大于6时，复合物凝胶的BSA释放加速，复合物凝胶收缩。在pH 8.8，高于乳铁蛋白等电点时，观察到乳铁蛋白的持续释放。这些结果表明，凝胶与模型药物之间的静电相互作用影响了复合物凝胶的释放行为以及通过收缩而产生的挤压作用。在ph值大于6时，吲哚美辛从络合凝胶中缓释。因此，该复合凝胶可作为p - h控制的药物释放材料。

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.