饱和磷脂脂质体的室温下制备及其性质的研究  

LIPOSOME PREPARATION BY SATURATED PHOSPHOLIPID AT ROOM TEMPERATURE AND PROPERTIES OF THE LIPOSOMES

作　　者：王向涛[1] 杨天智[1] 李沙[1] 侯新朴[1] 

机构地区：[1]北京大学药学院药剂系,北京100083

出　　处：《药学学报》2002年第12期976-980,共5页Acta Pharmaceutica Sinica

摘　　要：目的　考察室温下用饱和磷脂制备脂质体的新方法 (加入特殊的附加剂 )及其对以蛋白多肽类为主药的包封情况 ,并研究了脂质体的体外性质。方法　通过加入特殊的附加剂 ,用反相蒸发 超声分散法制备脂质体 ,并初步考察了其室温放置的稳定性 ;以尿激酶为例 ,考察所得脂质体的粒度分布和形态 ;对不同的蛋白多肽类药物进行包封 ;以阿霉素为模型药物 ,考察脂质体在PBS和小牛血清中的泄漏。结果　附加剂DSPE PEG 2 0 0 0只需 1%的用量(占磷脂的摩尔比 ) ,即可用饱和磷脂在室温下超声 1min制得脂质体 ;所得脂质体平均粒径在 10 0nm以下 ,形态圆整 ,室温放置稳定 ;对胰岛素和水蛭素的包封率与普通脂质体相近 (2 3%) ,对尿激酶包封率高达 (6 5 4± 2 6 ) %;体外泄漏缓慢。结论　提出的制备方法条件温和 ,产品稳定性好 ,非常适合高分子量蛋白类药物 ,并可获得较高的包封率 ,是一种很有前景的脂质体制备方法。AIM To study the entrapment efficiency of different drugs (mainly proteins and polypeptides) in liposomes prepared by a new method using saturated phospholipids at room temperature and the in vitro properties of obtained liposomes. METHODS The liposomes was prepared by reverse phase evaporation in which a special adjunct was added. Urokinase and hirudin were fluorescene-labelled for determation of entrapment efficiency. The urokinase liposomes were used to observe the diameter distribution and the TEM photos; The leakage experiment of liposomes was done in PBS (phosphate buffered solution) and FCS (fatal calf serine). RESULTS The adjunct of only 0.2 mg·mL -1 and ultrasound time of only 1 min was enough to prepare liposomes at room temperature by saturated phospholipid; the liposomes were stable in storage, with the mean diameter under 100 nm and good shape; the entrapment efficiency was about 23% for hirudin and insulin, 65.44% for urokinase; the leaking rate of liposomes was slow either in PBS or in FCS at 37℃. CONCLUSION The preparation method was at mild conditions, gave stable products and was very stuitable for such drugs as proteins and polypeptides with high entrapment efficiency for high molecular proteins.

关 键 词：饱和磷脂 脂质体 附加剂 蛋白多肽 稳定性 包封率 制备方法 反相蒸发-超声分散技术 

分 类 号：R943[医药卫生—药剂学]