Hypoglycemic Effect of Intravenous Polyethylene Glycol-Coated Liposomal Insulin on Normal Rats  

正常大鼠静脉注射PEG包裹胰岛素脂质体的降血糖作用(英文)

作　　者：张煊[1] 张华[1] 王桂玲[1] 张大卫[1] 王静[1] 蔺伟[1] 张强[1] 

机构地区：[1]北京大学药学院药剂学系,北京,100083

出　　处：《Journal of Chinese Pharmaceutical Sciences》2004年第1期28-31,共4页中国药学（英文版）

基　　金：NationalNaturalScienceFundationofChina( 2 99925907)Correspondingauthor:Tel[phone])

摘　　要：Aim To evaluate liposome as an injectable delivery system of proteins, insulin was chosen as model drug and the hypoglycemic effect of PEG-coated liposomal insulin was tested.Methods The PEG-coated liposomal insulin was prepared by reversal-phase emulsion evaporation.For pharmacodynamic study, insulin (2.5 IU*kg-1) was intravenously administered in phosphated-buffered saline (PBS) solution, conventional liposomes, and PEG-coated liposomes, separately, to normal Wistar rats.Blood glucose levels were determined by the glucose oxidase method.Results The mean diameter of the PEG-coated liposomal insulin was 58.4 nm, while the encapsulation ratio reached 18.33%.After intravenous administration of insulin solution, insulin liposome, and PEG-coated liposomal insulin, the minimum blood glucose concentrations (Cmin %) reached 25.26±5.75%, 33.92±12.42%, and 42.39±10.5% of the initial level, respectively, and the time periods to reach the minimum blood glucose level (Tmin) were 0.7±0.3 h, 1.2±0.4 h, and 2.3±0.7 h, respectively.The relative pharmacological bioavailabilities of insulin liposome and PEG-coated liposomal insulin were 98.03% and 99.70%, respectively, compared with the control of insulin solution.Conclusion PEG-coated liposome can be developed as a relatively sustained injectable delivery system for insulin.Moreover, the liposome coated with PEG may have advantages over normal liposome.目的　以胰岛素为模型药物 ,评价PEG包裹胰岛素脂质体的降血糖药效学作用。方法　采用逆相蒸发法制备PEG包裹的胰岛素脂质体。正常Wistar大鼠分别静脉注射给予胰岛素溶液、胰岛素脂质体及PEG包裹的胰岛素脂质体。采用葡萄糖还原酶法测定血清中的血糖浓度。以梯形法计算血糖 -时间曲线上面积 (AAC) ,采用胰岛素溶液的AAC为对照 ,分别计算胰岛素脂质体和PEG包裹的胰岛素脂质体的药理相对生物利用度。结果　PEG包裹的胰岛素脂质体的包封率为 18 3 3 % ,平均粒径为 58 4nm。静脉注射给予胰岛素溶液、胰岛素脂质体和PEG包裹的胰岛素脂质体后 ,其血糖降低的最低百分率(Cmin% )分别为 :2 5 2 6± 5 75% ,3 3 92± 12 42 %和 42 3 9± 10 5% ;达到最低百分率的时间 (Tmin)分别为 :0 7± 0 3 ,1 2± 0 4和 2 3± 0 7h。胰岛素脂质体和PEG包裹的胰岛素脂质体的药理相对生物利用度分别为 :98 0 3 %和 99 70 %。结论　PEG包裹的胰岛素脂质体具有相对的缓释作用 。

关 键 词：INSULIN polyethylene glycol-coated liposome PHARMACODYNAMICS 

分 类 号：R977.15[医药卫生—药品]