Interaction of positively-charged liposomes with blood: implications for their application in vivo.
Interaction of positively-charged liposomes with blood: implications for their application in vivo.
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DOI：
10.1016/0005-2736(91)90160-a
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发表时间：
1991-11
期刊：
影响因子：
--
通讯作者：
J. Senior;K. Trimble;R. Maskiewicz
中科院分区：
文献类型：
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作者：
J. Senior;K. Trimble;R. Maskiewicz
带正电脂质成分的脂质体先前已在人类疾病的动物模型中证明了功效，目前正在人类临床研究中进行评估。阳离子脂质可以提高药物和其他带负电荷物质的包裹效率，并促进体外生物膜的渗透，例如转染。然而，含有硬脂胺的带正电脂质体也有毒性作用的报道。在本报告中，我们检查了血浆成分或红细胞与富含胆固醇的SUV（由PC或DPPC组成）之间的总体相互作用，并将0-50 mol%的磷脂替换为带正电的硬脂胺、DOTMA或BisHOP。观察到的等离子体相互作用包括通常透明的间质浑浊度增加和/或血栓样肿块的形成。当血浆浓度为0.25 μmol/ml或更高时，血浆相互作用的程度取决于正电荷的浓度、脂质体中最初存在的阳离子脂质的电荷密度，以及提供正电荷的脂质的性质。当脂质体正电荷浓度为0.5 μmol/ml时，硬脂胺引起血浆浊度的强烈增加，而含有DOTMA或BisHOP的脂质体引起强烈的凝血反应。体外红细胞素与阳离子脂质体相互作用时发生溶血，其中正电荷由DOTMA或硬脂胺贡献，而不是BisHOP。对含阳离子脂质脂质体的临床应用意义进行了讨论。
Liposomes with positively-charged lipid components have previously demonstrated efficacy in animal models for human diseases, and are currently being evaluated in human clinical studies. Cationic lipids can improve entrapment efficiency of drugs and other substances which are negatively charged, and facilitate penetration of biological membranesin vitro, e.g. in transfection. However, toxic effects have also been reported for positively-charged liposomes containing stearylamine. In this report we have examined gross interactions between plasma components or erythrocytes with cholesterol-rich SUV composed of PC or DPPC and having 0–50 mol% of phospholipid replaced with positively-charged stearylamine, DOTMA, or BisHOP. Plasma interactions observed included increased turbidity of the usually clear stroma and/or formation of a clot-like mass. At plasma concentrations of 0.25 μmol/ml or more, the extent of plasma interactions depended upon the concentration of positive charge, the charge density of cationic lipid initially present in the liposomes, and to a lesser degree, the nature of the lipid providing the positive charge. At liposomal positive charge concentrations of >0.5 μmol/ml plasma, stearylamine provoked a strong increase in plasma turbidity, whereas liposomes incorporating DOTMA or BisHOP provoked a strong clotting response. Some hemolysis of erythrocytesin vitrooccurred on interaction with cationic liposomes where positive charge was contributed by DOTMA or stearylamine, but not BisHOP. Implications for the clinical use of liposomes containing cationic lipids, is discussed.