State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, Shanghai 200438, China.
J Mater Chem B. 2021 Aug 21;9(31):6234-6245. doi: 10.1039/d1tb00806d. Epub 2021 Jul 30.
Diabetes mellitus is the most common metabolic disease in the world. Herein, insulin- and cholic acid-loaded zein nanoparticles with dextran surfaces were fabricated to enhance the oral absorptions of insulin in the intestine and in the liver which is the primary action organ of endogenous insulin. In the nanoparticles, zein acted as cement to embed insulin, cholic acid and casein by hydrophobic interactions. The hydrophilic dextran conjugated to casein by the Maillard reaction was located on the nanoparticle surface. The nanoparticles had an insulin loading efficiency of 74.6%, a cholic acid loading efficiency of 55.1% and a hydrodynamic diameter of 267 nm. The dextran significantly increased the disperse stability of the nanoparticles, protected the loaded insulin from hydrolysis in digestive juices, and increased the trans-mucus permeability of the insulin. The embedded cholic acid molecules were consecutively exposed to the surface when the nanoparticles were gradually eroded by proteases. The exposed cholic acid promoted the absorptions of the nanoparticles in the ileum and liver via bile acid transporters. The effect of pretreated lymphatic transport inhibitor cycloheximide revealed that about half of the nanoparticles were transported via the intestinal lymphatic transport pathway and the other half of the nanoparticles were transported via portal blood absorption. The oral pharmacological bioavailability of the nanoparticles in type I diabetic mice was 12.5-20.5%. This study demonstrates that nanoparticles are a promising oral delivery system for insulin.
糖尿病是世界上最常见的代谢性疾病。本文构建了载胰岛素和胆酸的具有葡聚糖表面的玉米醇溶蛋白纳米粒，以增强胰岛素在肠道和肝脏（内源性胰岛素的主要作用器官）中的口服吸收。在纳米粒中，玉米醇溶蛋白通过疏水相互作用作为水泥将胰岛素、胆酸和酪蛋白嵌入其中。通过美拉德反应与酪蛋白连接的亲水性葡聚糖位于纳米粒表面。纳米粒的胰岛素载药效率为 74.6%，胆酸载药效率为 55.1%，水动力直径为 267nm。葡聚糖显著提高了纳米粒的分散稳定性，保护了载药胰岛素免受消化液的水解，并增加了胰岛素的跨黏膜通透性。当纳米粒被蛋白酶逐渐侵蚀时，嵌入的胆酸分子依次暴露于表面。暴露的胆酸通过胆汁酸转运蛋白促进了纳米粒在回肠和肝脏中的吸收。预处理的淋巴转运抑制剂环己亚胺的作用表明，约一半的纳米粒通过肠淋巴转运途径运输，另一半纳米粒通过门静脉血液吸收运输。在 I 型糖尿病小鼠中的口服药代动力学生物利用度为 12.5-20.5%。本研究表明，纳米粒是胰岛素口服递送的一种有前途的系统。
