西红柿凝集素修饰脂质体对小鼠口服吸收胰岛素的促进作用

The enhancing effect of tomato lectin modified liposomes of insulin on oral absorption in mice

目的 研究西红柿凝集素修饰的胰岛素脂质体在小鼠胃肠道吸收作用。方法 采用碳二亚胺交联法制备西红柿凝集素(TL)修饰的磷脂酰乙醇胺(PR),将TL-PE掺入胰岛素脂质体中制成凝集素修饰脂质体并证实TL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350μ·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 正常小鼠中,西红柿凝集素修饰脂质体在4h血糖降至初始水平的(85±5)％,8h降至(54±11)％,12h为(57±6)％。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。糖尿病模型小鼠中,西红柿凝集素修饰脂质体在4h血糖降至初始水平的(38±13)％,8h降至(50±15)％,12h为(50±16)％。结论 西红柿凝集素修饰的脂质体可能通过与细胞表面特异性受体的结合作用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 tomato lectin (TL) modified liposomes as the carrier. Methods TL-phosphatidylethanolamine (PE) conjugate (TL-PE) was synthesized by using carbodiimide cross-linking method, then the compound was incorporated into the conventional liposomes of insulin. The agglutination test was performed to examine TL biological activities after synthesis and incorporation. When TL modified liposomes were administrated orally to the normal mice or diabetic mice at insulin dose of 350 u·kg^(-1), the hypoglycemic effect was determinated according to the blood glucose level. Results The blood glucose levels of the normal mice were reduced by modified liposomes. The glucose levels were (85±5)% at 4 h, (54±11)% at 8 h, (57±6)% at 12 h postdose compared with the glucose levels prior to oral administration respectively. However, the conventional liposomes and saline have no hypoglycemic effect. The blood glucose levels of the diabetic mice were obviously reduced by TL modified liposomes, the glucose levels were (38±13)% at 4 h, (50±15)% at 8 h, (50± 16)% at 12 h respectively. Conclusion TL modified liposomes promote the oral absorption of insulin due to the specific-site combination on GI cell membrane.