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由1,2 - 二油酰基 - 3 - 三甲基氯化铵丙烷(DOTAP)和磷脂酰胆碱组成的阳离子囊泡及其与红细胞膜的相互作用。

Cationic vesicles consisting of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and phosphatidylcholines and their interaction with erythrocyte membrane.

作者信息

Kitagawa Shuji, Kasamaki Masatoshi, Hyodo Megumi

机构信息

Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Japan.

出版信息

Chem Pharm Bull (Tokyo). 2004 Apr;52(4):451-3. doi: 10.1248/cpb.52.451.

Abstract

We studied the formation and stability of vesicles consisting of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and phosphatidylcholines by electron spin resonance (ESR) analysis and observation of their hemolytic activities. In contrast with previous findings on dimethyldialkylammoniums, DOTAP formed vesicles at 37 degrees C with phosphatidylcholines containing either saturated acyl chains such as dimyristoylphosphatidylcholine (DMPC) or unsaturated acyl chains such as dilinoleoylphosphatidylcholine (DLPC). Phosphatidylcholines made the bilayer more rigid and significantly reduced the hemolytic activity of DOTAP. In the presence of equimolar concentration of DOTAP and phosphatidylcholines, formation of tightly aggregated structures of several erythrocytes was observed, as previously reported for the vesicles containing dimethyldipalmitylammonium. These findings indicate that DOTAP vesicles were stabilized by phosphatidylcholines with either saturated acyl chains or unsaturated acyl chains, and the interaction with the lipid bilayer of biological membranes as cationic vesicles became prominent with minimal membrane damage by DOTAP monomers.

摘要

我们通过电子自旋共振(ESR)分析及其溶血活性观察,研究了由1,2 - 二油酰基-3 - 三甲基铵丙烷(DOTAP)和磷脂酰胆碱组成的囊泡的形成和稳定性。与先前关于二甲基二烷基铵的研究结果相反,DOTAP在37℃下与含有饱和酰基链(如二肉豆蔻酰磷脂酰胆碱(DMPC))或不饱和酰基链(如二亚油酰磷脂酰胆碱(DLPC))的磷脂酰胆碱形成囊泡。磷脂酰胆碱使双层更具刚性,并显著降低了DOTAP的溶血活性。在等摩尔浓度的DOTAP和磷脂酰胆碱存在下,观察到几个红细胞形成紧密聚集的结构,这与先前报道的含有二甲基二棕榈酰铵的囊泡情况相同。这些发现表明,DOTAP囊泡通过含有饱和酰基链或不饱和酰基链的磷脂酰胆碱得以稳定,并且作为阳离子囊泡与生物膜脂质双层的相互作用变得显著,同时DOTAP单体对膜的损伤最小。

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