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
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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 2000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1 min制得脂质体;所得脂质体平均粒径在100 nm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(23%),对尿激酶包封率高达(65.4±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。Abstract: AIMTo 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. METHODSThe 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). RESULTSThe 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℃. CONCLUSIONThe 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.
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