摘要
目的 研究荆豆凝集素(UEA1)修饰的胰岛素脂质体在小鼠胃肠道的吸收作用。方法 采用碳二亚胺偶 联法制备荆豆凝集素修饰的磷脂酰乙醇胺(PE),将PE UEA1参入胰岛素脂质体中制成凝集素修饰脂质体,并证实 UEA1凝集活性不受影响。分别对正常小鼠及糖尿病模型小鼠灌胃给予350u·kg-1胰岛素的修饰脂质体溶液,用 葡萄糖酶试剂盒测定小鼠血糖,并与同剂量普通胰岛素脂质体比较。结果 对于正常小鼠,荆豆凝集素修饰脂质体 在4h使血糖降至初始水平的(84±15)%,8h降至(78±11)%,12h为(90±12)%。胰岛素普通脂质体几乎没有 降糖作用,与生理盐水对照组相当。对于糖尿病模型小鼠,荆豆凝集素修饰脂质体在4h使血糖降至初始水平的(73 ±7)%,8h降至(74±9)%,12h为(86±9)%。结论 荆豆凝集素修饰的脂质体可能通过与M细胞表面特异性受 体的结合促进大分子药物的胃肠吸收。
Aim To investigate the enhancing effect on insulin absorption through GI. tract in mice by using the Ulex europaeus agglutinin I (UEA1) modified liposomes as the carrier. Methods UEA1 modified phosphatidylethanolamine (PE) was prepared by conjugating method of 1-ethyl-3-(3′-dimethylaminopropyl) carbodiimide (EDC),then the modified compound (PE-UEA1) was incorporated into the conventional liposomes of insulin to obtain UEA1 modified liposomes. The agglutination test was performed to examine the UEA1 biological activities after synthesis and modification .When liposomes were applied to healthy mice or diabetic mice at insulin dose of 350 u·kg -1 orally,the hypoglycemic effect was investigated according to the blood glucose level determination. Results The blood glucose levels of the healthy mice reduced by UEA1 modified liposomes were (84±15)% at 4 h,(78±11)% at 8 h and (90±12)% at 12 h after oral administration. The conventional liposomes and saline showed no effect. The blood glucose levels of the diabetic mice reduced by UEA1 modified liposomes were (73±7)% at 4 h,(74±9)% at 8 h,(86±9)% at 12 h after oral administration. Conclusion The UEA1 modified liposomes promote the oral absorption of insulin due to the specific-site combination on M cell membrane.
出处
《药学学报》
CAS
CSCD
北大核心
2004年第12期1006-1010,共5页
Acta Pharmaceutica Sinica
基金
国家自然科学基金重点资助项目(39930200)
关键词
胰岛素
荆豆凝集素
脂质体
血糖
insulin
Ulex europaeus agglutinin I
liposomes
blood glucose
