Effective delivery system for oral insulin administration is a promising way for diabetes therapy. Herein, we prepared alginate microbeads containing chitosan nanoparticles (CNP) for controlled release of insulin. CNP was developed by reaction between tripolyphosphate (TPP) and chitosan. The ratio of TPP to chitosan was optimized aiming with smaller and more unified distributed CNP. TEM and DLS analysis confirmed that CNP has size around 150 nm with low PDI value and strong surface charge. Encapsulate ability for bovine serum albumin, working as model protein, was 11.45%, and the encapsulate efficiency was 23.70%. To modify the release profile of protein suitable for oral insulin delivery, sodium alginate was applied to coat on the surface of CNP by electrostatic interaction. After that, CaCl₂ was added to reinforce the alginate coating layer. FTIR analysis confirmed the interaction of alginate with chitosan and reaction with calcium ion. After reaction with Ca²⁺ ion, size measurement revealed that CNP was incorporated into alginate microbeads with mean diameter about 3.197 μm. Alginate microbeads presented irregular shape with small particles inside as revealed by optical microscope. Meanwhile, the release test demonstrated that protein release was pH-dependent. Acidic pH value retards protein release and neutral pH value promotes protein release. At last, insulin-loaded alginate microbeads were administrated to hyperglycemia model mice and blood glucose profile was monitored afterward. Insulin-loaded microbeads significantly lowered blood glucose level compared with mice treated with alginate microbeads without insulin. It is noted that insulin-loaded alginate microbeads could lower blood glucose level in much prolonged period of 96 h, indicating that insulin was released in controlled manner.

有效的口服胰岛素给药系统是糖尿病治疗的一种有前途的方法。本文中，我们制备了含有壳聚糖纳米颗粒（CNP）的藻酸盐微珠，用于控制胰岛素的释放。CNP是通过三聚磷酸（TPP）和壳聚糖之间的反应而开发的。针对TPP与壳聚糖的比例，针对较小，更统一的CNP进行了优化。TEM和DLS分析证实，CNP的尺寸约为150 nm，PDI值低，表面电荷强。作为模型蛋白的牛血清白蛋白的包封能力为11.45％，包封率为23.70％。为了改变适合口服胰岛素递送的蛋白质的释放曲线，通过静电相互作用将藻酸钠涂在CNP的表面上。之后，CaCl ₂加入水以增强藻酸盐涂层。FTIR分析证实了藻酸盐与壳聚糖的相互作用以及与钙离子的反应。与Ca ²⁺反应后离子的尺寸测量表明，CNP掺入了平均直径约为3.197μm的藻酸盐微珠中。光学显微镜显示藻酸盐微珠呈不规则形状，内部有小颗粒。同时，释放测试表明蛋白质释放是pH依赖性的。酸性pH值会延迟蛋白质的释放，而中性pH值会促进蛋白质的释放。最后，将胰岛素装载的藻酸盐微珠给予高血糖模型小鼠，然后监测血糖水平。与用不含胰岛素的藻酸盐微珠治疗的小鼠相比，胰岛素微珠显着降低了血糖水平。值得注意的是，负载胰岛素的藻酸盐微珠可在96小时的很长一段时间内降低血糖水平，表明胰岛素以受控方式释放。