Repulsive interactions and mechanical stability of polymer-grafted lipid membranes.
Repulsive interactions and mechanical stability of polymer-grafted lipid membranes.
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DOI：
10.1016/0005-2736(92)90112-y
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发表时间：
1992-07
期刊：
影响因子：
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通讯作者：
David C. Needham;T. J. McIntosh;Danilo D. Lasic
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文献类型：
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作者：
David C. Needham;T. J. McIntosh;Danilo D. Lasic
目前正在开发含有具有共价连接的聚（乙二醇）（PEG-脂质）的脂质的脂质体膜作为药物递送系统。这些所谓的“Stealth 20”脂质体在血液循环中具有相对较长的半衰期（101天），并显示出改变的体内生物分布。延长的寿命似乎是由于接枝聚合物对脂质体的空间稳定性。为了表征在这种聚合物接枝的脂质双层系统中促进空间稳定性的表面结构，我们已经使用X射线衍射来测量脂质/胆固醇（2：1）双层的结构组织和双层间排斥，所述双层并入4摩尔%的PEG-脂质，其中PEG部分的分子量为1900 g/mol。在此浓度下，施加的压力与双层间距离的关系表明，接枝聚合物部分从脂质表面延伸150 μ m，并产生了强大的，缓慢衰减的排斥压力膜之间，反对他们的密切的做法。此外，通过改变介质（1 mM NaCl和100 mM NaCl）的离子强度，仅适度改变压力与距离的关系。因此，即使PEG-脂质头基带有负电荷，长程压力也不能主要归因于静电双层压力。使用微量移液器操作的脂质双层弹性的测量表明，PEG-脂质没有改变脂质/胆固醇脂质体的内聚性质，这与X-射线结构数据一致，表明PEG-脂质没有改变双层内部的正常结构。从这些数据中，我们得出结论，脂质接枝的PEG聚合物链的排斥性屏障性质主要源于空间压力，并且这种简单的聚合物空间稳定性是聚合物接枝的脂质体观察到的延长的体内循环时间的基础。
Liposome membranes containing lipids with covalently attached poly(ethylene glycol)(PEG-lipid) are currently being developed as drug delivery systems. These, so called, ‘Stealth20’ liposomes have a relatively long half life (∼ 1day) in blood circulation and show an altered biodistributionin vivo. The extended lifetime appears to result from a steric stabilization of the liposome by the grafted polymer. In order to characterize the surface structures that promote steric stability in such polymer-grafted lipid bilayer systems, we have used X-ray diffraction to measure the structural organization and interbilayer repulsion for lipid/cholesterol (2:1) bilayers incorporating 4 mol% of a PEG-lipid in which the molecular weight of the PEG moiety was 1900 g/mol. At this concentration, applied pressure versus interbilayer distance relations showed that the grafted polymer moiety extended ∼ 50Åfrom the lipid surface and gave rise to a strong, slowly decaying repulsive pressure between membranes that opposed their close approach. Also, the pressure vs. distance relations were only modestly altered by changing the ionic strength of the medium (1 mM NaCl and 100 mM NaCl). Therefore, even though the PEG-lipid headgroup bears a negative charge, the long range pressure cannot be due primarily to an electrostatic double layer pressure. Measurements of lipid bilayer elasticity using micropipet manipulation showed that PEG-lipid did not change the cohesive properties of lipid/cholesterol liposomes which was consistent with the X-ray structural data showing that the PEG-lipid did not change the normal structure of the bilayer interior. From these data we concluded that the repulsive barrier properties of lipid-grafted PEG polymer chains originate mainly from a steric pressure and that this simple polymer steric stabilization is the basis for the extendedin vivocirculation times observed for polymer-grafted liposomes.