STRUCTURE AND PHASE-BEHAVIOR OF LIPID SUSPENSIONS CONTAINING PHOSPHOLIPIDS WITH COVALENTLY ATTACHED POLY(ETHYLENE GLYCOL)
STRUCTURE AND PHASE-BEHAVIOR OF LIPID SUSPENSIONS CONTAINING PHOSPHOLIPIDS WITH COVALENTLY ATTACHED POLY(ETHYLENE GLYCOL)
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DOI：
10.1016/s0006-3495(95)80368-1
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发表时间：
1995-05-01
影响因子：
3.4
通讯作者：
MCINTOSH, TJ
中科院分区：
文献类型：
--
作者：
KENWORTHY, AK;SIMON, SA;MCINTOSH, TJ
含有共价连接聚乙二醇的磷脂脂质体（peg -脂质体）正在被开发用于体内给药。本文研究了二硬脂酰磷脂酰胆碱（dsc）全水合悬浮液的结构和相行为，该悬浮液含有二硬脂酰磷脂酰乙醇胺和分子量为350 - 5000的peg组成的peg -脂质。对于含有0-60 mol % PEG-脂质的dsc:PEG-脂质悬浮液，差示扫描量热法显示主要吸热转变范围为55至64℃，这取决于PEG的大小和PEG-脂质浓度。这一主要转变的焓在所有PEG-350浓度下保持不变，但随着PEG-750、PEG-2000或PEG-5000浓度的增加而降低，最终在peg -脂质浓度大于约60 mol %时消失。低角x射线衍射和广角x射线衍射结果表明，在浓度约为10 mol %或更低时，所有PEG-脂质分子量均形成倾斜的凝胶（L β′）相双分子层，双分子层之间的距离取决于PEG分子量和PEG-脂质浓度。当PEG-脂质浓度大于10mol %时，脂质结构取决于PEG片段的大小。x射线衍射分析表明，当含有40-100 mol %的PEG-350或20-70 mol %的PEG-750时，可形成未分离的交叉指状（L β 1）凝胶相双分子层；当含有20-60 mol %的PEG-2000和PEG-5000时，可形成未分离的凝胶相双分子层。光学显微镜，浊度测量，x射线衍射和h -1核磁共振表明，在超过60%的PEG-750， PEG-2000或PEG-5000存在下形成纯胶束相。
Liposomes containing phospholipids with covalently attached poly(ethylene glycol) (PEG-lipids) are being developed for in vivo drug delivery. In this paper we determine the structure and phase behavior of fully hydrated distearoylphosphatidylcholine (DSPC) suspensions containing PEG-lipids composed of distearoylphosphatidylethanolamine with attached PEGs of molecular weights ranging from 350 to 5000. For DSPC:PEG-lipid suspensions containing 0-60 mol % PEG-lipid, differential scanning calorimetry shows main endothermic transitions ranging from 55 to 64 degrees C, depending on the size of the PEG and concentration of PEG-lipid. The enthalpy of this main transition remains constant for ail PEG-350 concentrations but decreases with increasing amounts of PEG-750, PEG-2000, or PEG-5000, ultimately disappearing at PEG-lipid concentrations greater than about 60 mol %. Low-angle and wide-angle x-ray diffraction show that tilted gel (L beta') phase bilayers are formed for all PEG-lipid molecular weights at concentrations of about 10 mol % or less, with the distance between bilayers depending on PEG molecular weight and PEG-lipid concentration. At PEG-lipid concentrations greater than 10 mol %, the lipid structure depends on the size of the PEG moiety. X-ray diffraction analysis shows that untilted interdigitated (L beta l) gel phase bilayers form with the incorporation of 40-100 mot % PEG-350 or 20-70 mol % PEG-750, and untilted gel (L beta) phase bilayers are formed in the presence of about 20-60 mol % PEG-2000 and PEG-5000. Light microscopy, turbidity measurements, x-ray diffraction, and H-1-NMR indicate that a pure micellar phase forms in the presence of greater than about 60% PEG-750, PEG-2000, or PEG-5000.