Key Laboratory of Smart Drug Delivery, School of Pharmacy, Fudan University, Shanghai, PR China.
Eur J Pharm Biopharm. 2012 Jun;81(2):265-72. doi: 10.1016/j.ejpb.2012.02.009. Epub 2012 Feb 18.
Oral delivery of protein or polypeptide drugs remains a challenge due to gastric and enzymatic degradation as well as poor permeation across the intestinal epithelia. In this study, liposomes containing bile salts were developed as a new oral insulin delivery system. The primary goal was to investigate the effect of cholate type, particle size and dosage of the liposomes on the hypoglycemic activity and oral bioavailability. Liposomes containing sodium glycocholate (SGC), sodium taurocholate (STC) or sodium deoxycholate (SDC) were prepared by a reversed-phase evaporation method. After oral administration, all liposomes elicited a certain degree of hypoglycemic effect in parallel with an increase in blood insulin level. The highest oral bioavailability of approximately 8.5% and 11.0% could be observed with subcutaneous insulin as reference for SGC-liposomes in non-diabetic and diabetic rats, respectively. Insulin-loaded liposomes showed slower and sustained action over a period of over 20 h with peak time around 8-12h. SGC-liposomes showed higher oral bioavailability than liposomes containing STC or SDC and conventional liposomes. The hypoglycemic effect was size-dependent with the highest at 150 nm or 400 nm and was proportionally correlated to the administered dose. The results supported the hypothesis of insulin absorption as intact liposomes.
由于胃内降解和酶降解以及肠上皮通透性差，蛋白质或多肽类药物的口服递送仍然是一个挑战。在这项研究中，开发了含有胆汁盐的脂质体作为一种新的口服胰岛素递送系统。主要目标是研究胆酸盐类型、脂质体粒径和剂量对降血糖活性和口服生物利用度的影响。采用反相蒸发法制备了含有甘胆酸钠（SGC）、牛磺胆酸钠（STC）或脱氧胆酸钠（SDC）的脂质体。口服给药后，所有脂质体均在一定程度上引起血糖降低，同时血胰岛素水平升高。以皮下胰岛素为参照，非糖尿病和糖尿病大鼠中 SGC-脂质体的口服生物利用度最高分别约为 8.5%和 11.0%。胰岛素负载的脂质体在超过 20 小时的时间内显示出较慢和持续的作用，峰值时间约为 8-12 小时。SGC-脂质体的口服生物利用度高于含有 STC 或 SDC 的脂质体和常规脂质体。降血糖作用与粒径有关，在 150nm 或 400nm 时最高，并与给药剂量成正比。结果支持了胰岛素作为完整脂质体吸收的假说。
