School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210046, China.
School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210046, China.
J Pharm Sci. 2021 Jan;110(1):268-279. doi: 10.1016/j.xphs.2020.07.004. Epub 2020 Jul 12.
The aim of the study is to design octaarginine (R8)-modified insulin-alginate nanoparticles (INS-SA/R8 NPs) as the oral insulin delivery system, and further investigate its penetrating mechanism. The characterization results indicated that the surface of INS-SA/R8 NPs was smooth and the average diameter was about 300 nm. INS-SA/R8 NPs exhibited a stronger stability in the simulated gastrointestinal fluids and had a better controlled release than unmodified alginate nanoparticles (INS-SA NPs). Moreover, INS-SA/R8 NPs group had the strongest insulin transport capacity and the largest amount of insulin uptake in all experimental groups. Most importantly, the improvement of insulin intestinal uptake was further confirmed in rat intestine in vivo, and its penetrating mechanism might be involved in the production of endogenous nitric oxide (NO) signal molecule. In addition, in vivo hypoglycemic studies showed that orally administrated INS-SA/R8 NPs produced a better hypoglycemic effect as compared with INS-SA NPs in diabetic rats. Meanwhile, from the cytotoxicity analysis, INS-SA/R8 NPs were safe for oral administration. Taken together, INS-SA/R8 NPs was a good oral insulin delivery system, which might also be suitable for other protein drugs.
本研究旨在设计八精氨酸（R8）修饰的胰岛素-海藻酸钠纳米粒（INS-SA/R8 NPs）作为口服胰岛素递药系统，并进一步研究其渗透机制。表征结果表明，INS-SA/R8 NPs 表面光滑，平均直径约为 300nm。与未修饰的海藻酸钠纳米粒（INS-SA NPs）相比，INS-SA/R8 NPs 在模拟胃肠液中具有更强的稳定性和更好的控制释放能力。此外，INS-SA/R8 NPs 组具有最强的胰岛素转运能力和所有实验组中最大的胰岛素摄取量。最重要的是，在体内大鼠肠中进一步证实了胰岛素肠道摄取的改善，其渗透机制可能涉及内源性一氧化氮（NO）信号分子的产生。此外，体内降血糖研究表明，与 INS-SA NPs 相比，口服给予 INS-SA/R8 NPs 可在糖尿病大鼠中产生更好的降血糖效果。同时，从细胞毒性分析来看，INS-SA/R8 NPs 口服给药安全。综上所述，INS-SA/R8 NPs 是一种良好的口服胰岛素递药系统，也可能适用于其他蛋白质药物。
