Oral delivery of protein or peptide drugs confronts several barriers, the intestinal epithelium and the mucus barrier on the gastrointestinal tract is deemed to be the toughest obstacles. However, overcoming these two obstacles requires contradictory surface properties of a nanocarrier. In the present work, mesoporous silica nanoparticles (MSNs) were modified with deoxycholic acid (DC) and coated with sulfobetaine 12 (SB12) for the first time to achieve both improved mucus permeation and transepithelial absorption. MSNs modified with stearic acid and coated with dilauroylphosphatidylcholine (DLPC) or Pluronic P123 were also prepared as controls. The SB12 coated DC modified MSN had high drug loading of 22.2%. The zwitterion coating endows the MSN improved mucus penetrating ability. In addition, the carrier also showed remarkable affinity with epithelial cells. The cellular uptake was significantly improved (10-fold for Caco-2 cells and 8-fold for E12 cells). The results also indicated that the DC modified carrier was able to avoid entry into lysosomes. It can increase the absorption of loaded insulin in all intestine segments and showed outstanding hypoglycemic effect in diabetic rats. The results suggest the zwitterion-functionalized MSNs might be a good candidate for oral protein delivery.

蛋白质或肽类药物的口服给药面临几个障碍，肠上皮和胃肠道粘液障碍被认为是最困难的障碍。然而，克服这两个障碍需要纳米载体的矛盾的表面性质。在目前的工作中，介孔二氧化硅纳米粒子（MSNs）用脱氧胆酸（DC）进行了修饰，并首次用磺基甜菜碱12（SB12）涂覆，以实现改善的粘液渗透和跨上皮吸收。还制备了用硬脂酸修饰并涂有二月桂酰磷脂酰胆碱（DLPC）或Pluronic P123的MSN作为对照。SB12包被的DC修饰的MSN具有22.2％的高载药量。两性离子涂层赋予MSN改善的粘液穿透能力。此外，载体还显示出与上皮细胞的显着亲和力。细胞摄取显着改善（Caco-2细胞为10倍，E12细胞为8倍）。结果还表明，DC修饰的载体能够避免进入溶酶体。它可以增加所有肠段中负载胰岛素的吸收，并在糖尿病大鼠中表现出出色的降血糖作用。结果表明，两性离子官能化的MSN可能是口服蛋白质递送的良好候选者。