Abstract：
Soybean phospholipid was used as an amphiphilic material to form reverse micelles (RMs) in medium glycerol monolinoleate (Maisine) with Exenatide (EXT.) encapsulated in the polar core formed by the hydrophilic part of phospholipid. Cremopher RH40 and caprylocaproyl macrogol-8 glycerides EP/caprylocaproyl polyoxyl-8 glycerides NF (Labrasol) were added as surfactants to prepare reverse micelles-self emulsifying drug delivery system (RMs-SEDDS). On this basis, oil in water (O/W) emulsion was further prepared. By adding DOTAP, the surface of the emulsion was positively charged. Finally, hyaluronic acid wrapping in the outermost layer by electrostatic adsorption and reverse micelles-O/W-sodium hyaluronate (RMs-O/W-HA) nanoparticles containing Exenatide were prepared. RMs-SEDDS was spherical with an average particle size of 213.6 nm and RMs-O/W-HA was double-layered spherical nanoparticle with an average particle size of 309.2 nm. HA coating enhanced the adhesion of nanoparticles (NPs), and RMs-O/W-HA increased cellular uptake through CD44-mediated endocytosis. Pharmacodynamics results showed that RMs-SEDDS and RMs-O/W-HA could reduce blood glucose in type 2 diabetic rats, protect pancreatic β cells to a certain extent, and relieve insulin resistance and hyperlipemia complications with good safety.
摘要：
大豆磷脂用作两亲材料，在中等甘油单油酸酯（Maisine）与艾塞那肽（EXT。）封装在由磷脂的亲水部分形成的极性核心中。添加CremopherRH40和辛丙酰基聚乙二醇-8甘油酯EP/辛丙酰基聚氧乙烯-8甘油酯NF（Labrasol）作为表面活性剂，以制备反胶束-自乳化药物递送系统（RM-SEDDS）。在此基础上,进一步制备水包油型(O/W)乳液。通过添加DOTAP，乳液的表面带正电荷。最后,通过静电吸附将透明质酸包裹在最外层，并制备了含有艾塞那肽的反胶束-O/W-透明质酸钠（RMs-O/W-HA）纳米颗粒。RMs-SEDDS为球形，平均粒径为213.6nm，RMs-O/W-HA为双层球形纳米颗粒，平均粒径为309.2nm。HA涂层增强了纳米颗粒（NPs）的附着力，和RMs-O/W-HA通过CD44介导的内吞作用增加细胞摄取。药效学结果显示RMs-SEDDS和RMs-O/W-HA能降低2型糖尿病大鼠的血糖,在一定程度上保护胰岛β细胞,减轻胰岛素抵抗和高脂血症并发症，安全性好。
