Oral insulin delivery is considered a revolutionary alternative to daily subcutaneous injections in terms of compliance and convenience. However, significant challenges remain in terms of inactivation in gastrointestinal environment and limited permeation across the intestinal epithelium. Herein, we used acid-resistant metal-organic framework (PCN-222) to load insulin and modified the exterior with sodium dodecyl sulfate (SDS) to achieve efficient oral insulin delivery. The PCN-222 nanocarrier with ordered mesoporous cage structure and suitable pore size achieved a high insulin loading of 75 %. The SDS on the surface of nanocarrier reduces its hydrophilicity while reversibly altering cell morphology and increasing epithelial cell permeability, thereby promoting intestinal epithelial absorption. The constructed particle (I@P@S) was encapsulated in sodium alginate (SA) microspheres to protect it from gastric acid degradation and releases it upon entry into the intestinal tract. Through an uptake pathway dominated by clathrin-mediated endocytosis, the released I@P@S realized efficient intestinal permeability and controlled insulin release under physiological conditions due to the phosphate sensitivity of PCN-222, leading to an in vivo bioavailability of 12.9 %. This work provides a valuable reference for the design of oral insulin delivery systems.

中文翻译：

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基于耐酸金属有机框架的环境响应平台，用于高效口服胰岛素输送


口服胰岛素输送在依从性和便利性方面被认为是日常皮下注射的革命性替代方案。然而，在胃肠道环境中的失活和肠上皮的有限渗透方面仍然存在重大挑战。在此，我们使用耐酸金属有机框架 （PCN-222） 加载胰岛素，并用十二烷基硫酸钠 （SDS） 修饰外部以实现高效的口服胰岛素输送。具有有序介孔笼结构和合适孔径的 PCN-222 纳米载体实现了 75% 的高胰岛素负载。纳米载体表面的 SDS 降低了其亲水性，同时可逆地改变了细胞形态并增加了上皮细胞通透性，从而促进了肠上皮吸收。构建的颗粒 （I@P@S） 被封装在海藻酸钠 （SA） 微球中，以保护其免受胃酸降解，并在进入肠道时释放。通过 clathrin 介导的内吞作用主导的摄取途径，由于 PCN-222 的磷酸盐敏感性，释放的I@P@S在生理条件下实现了有效的肠道通透性和受控的胰岛素释放，导致体内生物利用度为 12.9%。这项工作为口服胰岛素输送系统的设计提供了有价值的参考。