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[脂质体作为潜在药物载体对磷脂酶A2作用的抗性]

[The resistance of liposomes as potential drug carriers to the action of phospholipase A2].

作者信息

Litvinko N M, Shumilina T A, Naubatova M K, Akhrem A A

出版信息

Prikl Biokhim Mikrobiol. 1993 May-Jun;29(3):478-84.

PMID:8516280
Abstract

Stability of liposomes with varied phospholipid (PL) content towards the action of phospholipase A2 (PLA2) was studied in vitro. Liposomes were prepared of phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) and their mixtures with sphingomyelin (SM). PC and PG liposomes were also treated with PLA2 in the presence of a number of proteins such as cytochrome c, cytochrome b5, cytochrome P-450, polylysine, and histone H1. Among all the liposomes studied PG-containing ones were found to be most stable towards PLA2. In SM-containing liposomes, the levels of PG, PI, PE and PC after 20 min of hydrolysis were 65, 62, 55 and 50%, respectively. In PC + PG liposomes, the PC content after treatment with PLA2 was by about 15-20% higher than in control PC liposomes. The addition of all the proteins studied influenced significantly stability of both PC and PG in two-component PL liposomes, but had no effect on liposomes consisting only of PC. The incorporation of the integral membrane protein cytochrome P-450 into PC and PG liposomes caused a decrease in their stability towards PLA2, the decrease depending on the lipid/protein molar ratio.

摘要

体外研究了不同磷脂(PL)含量的脂质体对磷脂酶A2(PLA2)作用的稳定性。脂质体由磷脂酰胆碱(PC)、磷脂酰甘油(PG)、磷脂酰乙醇胺(PE)、磷脂酰肌醇(PI)以及它们与鞘磷脂(SM)的混合物制备而成。PC和PG脂质体还在多种蛋白质如细胞色素c、细胞色素b5、细胞色素P - 450、聚赖氨酸和组蛋白H1存在的情况下用PLA2处理。在所有研究的脂质体中,含PG的脂质体对PLA2最稳定。在含SM的脂质体中,水解20分钟后PG、PI、PE和PC的水平分别为65%、62%、55%和50%。在PC + PG脂质体中,用PLA2处理后PC含量比对照PC脂质体高约15 - 20%。所研究的所有蛋白质的添加都显著影响了双组分PL脂质体中PC和PG的稳定性,但对仅由PC组成的脂质体没有影响。将整合膜蛋白细胞色素P - 450掺入PC和PG脂质体导致它们对PLA2的稳定性降低,降低程度取决于脂质/蛋白质摩尔比。

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