Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Biomaterials. 2010 Apr;31(12):3384-94. doi: 10.1016/j.biomaterials.2010.01.042. Epub 2010 Feb 10.
A pH-sensitive nanoparticle (NP) system composed of chitosan and poly(gamma-glutamic acid) was prepared for the oral delivery of insulin. The biodistribution study in a rat model showed that some of the orally administered NPs were retained in the stomach for a long duration, which might lead to the disintegration of NPs and degradation of insulin. To overcome these problems, we freeze-dried NPs and filled them in an enteric-coated capsule. The small angle X-ray scattering (SAXS) profiles indicated that the freeze-drying process did not significantly disrupt the internal structure of NPs; additionally, their pH-sensitivity was preserved and the insulin release was pH-dependent. The results obtained in the native PAGE analysis indicated that the released insulin molecules were neither fragmented nor aggregated. Upon oral administration, the enteric-coated capsule remained intact in the acidic environment of the stomach, but dissolved rapidly in the proximal segment of the small intestine. Consequently, all the NPs loaded in the capsule were brought into the small intestine, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. The relative bioavailability of insulin was found to be approximately 20%. These results suggest that the formulation developed in the study might be employed as a potential approach for the oral delivery of insulin.
一种由壳聚糖和聚（γ-谷氨酸）组成的 pH 敏感纳米颗粒（NP）系统被制备用于胰岛素的口服递送。在大鼠模型中的体内分布研究表明，一些口服给予的 NPs 在胃中长时间保留，这可能导致 NPs 的崩解和胰岛素的降解。为了克服这些问题，我们将 NPs 冷冻干燥并填充在肠溶胶囊中。小角 X 射线散射（SAXS）谱表明，冷冻干燥过程并未显著破坏 NPs 的内部结构；此外，它们的 pH 敏感性得以保留，并且胰岛素的释放是 pH 依赖性的。天然 PAGE 分析的结果表明，释放的胰岛素分子既没有碎片化也没有聚集。口服给予时，肠溶胶囊在胃的酸性环境中保持完整，但在小肠的近端迅速溶解。因此，胶囊中装载的所有 NPs 都被带入小肠，从而增强了胰岛素的肠道吸收，并提供了血糖水平的长时间降低。胰岛素的相对生物利用度约为 20%。这些结果表明，研究中开发的制剂可能被用作胰岛素口服递送的潜在方法。
