Phospholipid-cationic lipid interactions: influences on membrane and vesicle properties
Phospholipid-cationic lipid interactions: influences on membrane and vesicle properties
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DOI：
10.1016/s0005-2736(01)00290-5
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发表时间：
2001-05-02
影响因子：
3.4
通讯作者：
Straubinger, RM
中科院分区：
文献类型：
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作者：
Campbell, RB;Balasubramanian, SV;Straubinger, RM
由合成的二烷基阳离子脂质和两性离子磷脂如二油酰磷脂酰乙醇胺组成的脂质体作为基因递送的载体已被广泛研究，但这些阳离子脂质体用于药物递送的更广泛潜力还没有。了解磷脂-阳离子脂质相互作用对于合理开发这种潜力至关重要。我们评估了阳离子脂质DOTAP（N-[1-（2，3-dioleoyloxy）propyl]-N，N，N-trimethylammonium）对脂质体物理性质如大小和膜结构域结构的影响。DSC（差示扫描量热法）显示在0.4- 20mol%范围内，随着DOTAP分数的增加，二棕榈酰磷脂酰胆碱（DPPC）的相变温度逐渐降低和加宽。膜结构域结构的荧光探针Laurdan（6-十二烷醇基-二甲基氨基-萘）显示，DOTAP和DPPC在所有测试比例下均保持混溶。DOTAP减少了自发形成的含PC的脂质体的大小，无论酰基链的长度和饱和度。阴离子脂质DOPG（dioleoylphosphatidylglycerol）对DPPC膜的流动性和大小有类似的影响。然而，与DOPG/DOPC（50/50）脂质体相反，DOTAP/DOPC（50/50）囊泡被OVCAR-3人卵巢肿瘤细胞贪婪地摄取。总的来说，DOTAP对双层物理性质产生了有效的影响，并可能为药物递送提供优势。(C)2001 Elsevier Science B. V.保留所有权利。
Liposomes composed of synthetic dialkyl cationic lipids and zwitterionic phospholipids such as dioleoylphosphatidyl-ethanolamine have been studied extensively as vehicles for gene delivery, but the broader potentials of these cationic liposomes for drug delivery have not. An understanding of phospholipid-cationic lipid interactions is essential for rational development of this potential. We evaluated the effect of the cationic lipid DOTAP (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium) on liposome physical properties such as size and membrane domain structure. DSC (differential scanning calorimetry) showed progressive decrease and broadening of the phase transition temperature of dipalmitoylphosphatidylcholine (DPPC) with increasing fraction of DOTAP, in the range of 0.4-20 mol%. Laurdan (6-dodecanolyl-dimethylamino-naphthalene), a fluorescent probe of membrane domain structure, showed that DOTAP and DPPC remained miscible at all ratios tested. DOTAP reduced the size of spontaneously-forming PC-containing liposomes, regardless of the acyl chain length and degree of saturation. The anionic lipid DOPG (dioleoylphosphatidylglycerol) had similar effects on DPPC membrane fluidity and size. However, DOTAP/DOPC (50/50) vesicles were taken up avidly by OVCAR-3 human ovarian tumor cells, in contrast to DOPG/DOPC (50/50) liposomes. Overall, DOTAP exerts potent effects on bilayer physical properties, and may provide advantages for drug delivery. (C) 2001 Elsevier Science B.V. All rights reserved.