Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China.
Int J Nanomedicine. 2012;7:3333-9. doi: 10.2147/IJN.S31711. Epub 2012 Jul 2.
The aim of this study was to design and characterize solid lipid nanoparticles (SLNs) modified with stearic acid-octaarginine (SA-R₈) as carriers for oral administration of insulin (SA-R₈-Ins-SLNs). The SLNs were prepared by spontaneous emulsion solvent diffusion methods. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the SA-R₈-Ins-SLNs were 162 nm, 29.87 mV, 3.19%, and 76.54%, respectively. The zeta potential of the SLNs changed dramatically, from -32.13 mV to 29.87 mV, by binding the positively charged SA-R₈. Morphological studies of SA-R₈-Ins-SLNs using transmission electron microscopy showed that they were spherical. In vitro, a degradation experiment by enzymes showed that SLNs and SA-R₈ could partially protect insulin from proteolysis. Compared to the insulin solution, the SA-R₈-Ins-SLNs increased the Caco-2 cell's internalization by up to 18.44 times. In the in vivo studies, a significant hypoglycemic effect in diabetic rats over controls was obtained, with a SA-R₈-Ins-SLN pharmacological availability value of 13.86 ± 0.79. These results demonstrate that SA-R₈-modified SLNs promote the oral absorption of insulin.
本研究旨在设计并表征硬脂酸-八精氨酸（SA-R₈）修饰的固体脂质纳米粒（SLNs）作为胰岛素（SA-R₈-Ins-SLNs）口服给药的载体。SLNs 通过自发乳化溶剂扩散法制备。SA-R₈-Ins-SLNs 的平均粒径、Zeta 电位、载药量和包封效率分别为 162nm、29.87mV、3.19%和 76.54%。通过结合带正电荷的 SA-R₈，SLNs 的 Zeta 电位从-32.13mV 急剧变化到 29.87mV。使用透射电子显微镜对 SA-R₈-Ins-SLNs 的形态学研究表明，它们呈球形。在体外，通过酶的降解实验表明，SLNs 和 SA-R₈ 可以部分保护胰岛素免受蛋白水解。与胰岛素溶液相比，SA-R₈-Ins-SLNs 使 Caco-2 细胞的内化增加了高达 18.44 倍。在体内研究中，糖尿病大鼠的降血糖作用明显优于对照组，SA-R₈-Ins-SLN 的药代动力学可用性值为 13.86±0.79。这些结果表明，SA-R₈ 修饰的 SLNs 促进了胰岛素的口服吸收。
