The oral delivery of insulin is a convenient and safe physiological route of administration for management of diabetes mellitus. In this study, we developed a poly-(styrene-co-maleic acid) (SMA) micellar system for oral insulin delivery to overcome the rapid degradation of insulin in the stomach, improve its absorption in the intestine, and provide a physiologically-relevant method of insulin to reach portal circulation. The insulin was encapsulated into SMA micelles in a pH-dependent process. The charge and size of the nanoparticles were determined by dynamic light scattering. The insulin loading of the nanoparticles was measured by HPLC. The transport of the SMA-insulin through biological membranes was assessed in vitro using Caco-2 cells, ex vivo rat intestinal section, and in vivo in a streptozotocin-induced diabetes mouse model. SMA-insulin micelles were negatively charged and had a mean diameter of 179.7 nm. SMA-insulin efficiently stimulated glucose uptake in HepG-2 hepatic cells and was transported across the Caco-2 epithelial cells in vitro by 46% and ex vivo across intestinal epithelium by 22%. The animal studies demonstrated that orally-administered SMA-insulin can produce a hypoglycemic effect up to 3 h after administration of one dose. Overall, our results indicate that SMA micelles are capable of the oral delivery of bioactive compounds like insulin and can be effective tools in the management of diabetes.

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在糖尿病小鼠模型中使用聚苯乙烯-顺丁烯二酸胶束的口服胰岛素递送

胰岛素的口服递送是用于糖尿病管理的方便且安全的生理给药途径。在这项研究中，我们开发了一种用于口服胰岛素递送的聚（苯乙烯-顺丁烯二酸）（SMA）胶束系统，以克服胰岛素在胃中的快速降解，提高其在肠道中的吸收并提供与生理相关的功能。胰岛素达到门脉循环的方法。胰岛素以pH依赖的过程被包裹在SMA胶束中。通过动态光散射确定纳米颗粒的电荷和尺寸。通过HPLC测量纳米颗粒的胰岛素负荷。在体外使用Caco-2细胞，离体大鼠肠道切片以及在链脲佐菌素诱导的糖尿病小鼠模型中体内评估了SMA胰岛素通过生物膜的转运。SMA-胰岛素胶束带负电，平均直径为179.7 nm。SMA-胰岛素有效地刺激了HepG-2肝细胞中的葡萄糖摄取，并在体外跨Caco-2上皮细胞转运了46％，离体跨肠上皮转运了22％。动物研究表明，口服一剂SMA胰岛素最多可在3小时内产生降血糖作用。总的来说，我们的结果表明SMA胶束能够口服递送生物活性化合物（如胰岛素），并且可以作为治疗糖尿病的有效工具。动物研究表明，口服一剂SMA胰岛素最多可在3小时内产生降血糖作用。总的来说，我们的结果表明SMA胶束能够口服递送生物活性化合物（如胰岛素），并且可以作为治疗糖尿病的有效工具。动物研究表明，口服一剂SMA胰岛素最多可在3小时内产生降血糖作用。总的来说，我们的结果表明SMA胶束能够口服递送生物活性化合物（如胰岛素），并且可以作为治疗糖尿病的有效工具。