Glucose-sensitive nano-films for insulin DDS

利用刀豆球蛋白A和糖原或合成的糖聚合物，基于逐层沉积的方法，成功地制备了葡萄糖敏感薄膜。薄膜的性能很大程度上取决于聚合物材料的化学结构。糖原在所有薄膜中具有最好的性能。糖原基膜在pH 7-9范围内稳定，在毫米级葡萄糖存在下几分钟即可分解。其他糖，如甘露糖和甲基化葡萄糖，也会导致膜的分解，这取决于糖与刀豆蛋白A的结合常数。为了评估胰岛素在纳米膜中的渗透性，我们将胰岛素包裹在纳米胶囊中，通过在含有胰岛素的碳酸钙表面逐层沉积聚电解质来监测胰岛素的释放行为。胰岛素从纳米胶囊中的释放速率取决于用于胶囊制备的聚合物材料的类型。用聚乙二亚胺制成的胶囊胰岛素释放迅速，而用聚烯丙基胺制成的胶囊释放速度相对较慢。聚烯丙基胺胶囊在30min后释放出约10%的胰岛素。相比之下，70%的胰岛素是从基于聚乙二亚胺的纳米胶囊中释放出来的。释药速率依赖于胶囊膜的厚度。因此，这些纳米膜可用于开发胰岛素的DDS系统。

Glucose-sensitive thin films have been successfully prepared using concanavalin A and glycogen or synthetic sugar polymers based on a layer-by-layer deposition. The properties of thin films significantly depended on the chemical structures of the polymeric materials. Glycogen afforded best property among the films. The glycogen-based films are stable in pH 7-9,and decomposed in a few minutes in the presence of glucose at mM level. Other sugars such as mannose and methylated glucose also induced decomposition of the films depending on the binding constants of the sugars to concanavalin A. The results can be explained reasonably based on a competitive binding of the sugars to concanavalin A in the films.In order to evaluate the permeability of insulin across the nano-films, insulin was encapsulated in nanocapsules which were fabricated by a layer-by-layer deposition of polyelectrolytes on the surface of calcium carbonate containing insulin and release behavior of the insulin was monitored. The release rate of insulin from the nanocapsules depended on the type of polymeric materials used for the capsule preparation. The insulin released rapidly from the capsules prepared using poly(ethyleneimine), while the release rate was relatively slow if the capsule was constructed using poly(allylamine). About 10% of insulin was released from the poly(allylamine)-based capsule after 30 min. In contrast, 70% of insulin was released from the poly(ethyleneimine)-based nanocapsule. The release rate was dependent on the thickness of the film of the capsules. Thus, it was demonstrated that these nano-films are useful for developing DDS systems for insulin.