Kenworthy A K, Simon S A, McIntosh T J
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Biophys J. 1995 May;68(5):1903-20. doi: 10.1016/S0006-3495(95)80368-1.
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 all 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 I) gel phase bilayers form with the incorporation of 40-100 mol % 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 1H-NMR indicate that a pure micellar phase forms in the presence of greater than about 60% PEG-750, PEG-2000, or PEG-5000.
含有共价连接聚乙二醇（PEG - 脂质）的磷脂的脂质体正被开发用于体内药物递送。在本文中，我们确定了完全水合的二硬脂酰磷脂酰胆碱（DSPC）悬浮液的结构和相行为，该悬浮液含有由二硬脂酰磷脂酰乙醇胺与分子量范围为350至5000的连接PEG组成的PEG - 脂质。对于含有0 - 60摩尔％PEG - 脂质的DSPC：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摄氏度，这取决于PEG的大小和PEG - 脂质的浓度。对于所有PEG - 350浓度，该主要转变的焓保持恒定，但随着PEG - 750、PEG - 2000或PEG - 5000量的增加而降低，最终在PEG - 脂质浓度大于约60摩尔％时消失。低角度和广角X射线衍射表明，对于所有PEG - 脂质分子量，在浓度约为10摩尔％或更低时形成倾斜的凝胶（Lβ'）相双层，双层之间的距离取决于PEG分子量和PEG - 脂质浓度。在PEG - 脂质浓度大于10摩尔％时，脂质结构取决于PEG部分的大小。X射线衍射分析表明，掺入40 - 100摩尔％PEG - 350或20 - 70摩尔％PEG - 750时形成未倾斜的交错（LβI）凝胶相双层，在存在约20 - 60摩尔％PEG - 2000和PEG - 5000时形成未倾斜的凝胶（Lβ）相双层。光学显微镜、浊度测量、X射线衍射和1H - NMR表明，在存在大于约60％的PEG - 750、PEG - 2000或PEG - 5000时形成纯胶束相。
