Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Langmuir. 2011 Jun 21;27(12):7788-98. doi: 10.1021/la200003n. Epub 2011 May 23.
We have combined Langmuir monolayer film experiments and all-atom molecular dynamics (MD) simulation of a bilayer to study the surface structure of a PEGylated liposome and its interaction with the ionic environment present under physiological conditions. Lipids that form both gel and liquid-crystalline membranes have been used in our study. By varying the salt concentration in the Langmuir film experiment and including salt at the physiological level in the simulation, we have studied the effect of salt ions present in the blood plasma on the structure of the poly(ethylene glycol) (PEG) layer. We have also studied the interaction between the PEG layer and the lipid bilayer in both the liquid-crystalline and gel states. The MD simulation shows two clear results: (a) The Na(+) ions form close interactions with the PEG oxygens, with the PEG chains forming loops around them and (b) PEG penetrates the lipid core of the membrane for the case of a liquid-crystalline membrane but is excluded from the tighter structure of the gel membrane. The Langmuir monolayer results indicate that the salt concentration affects the PEGylated lipid system, and these results can be interpreted in a fashion that is in agreement with the results of our MD simulation. We conclude that the currently accepted picture of the PEG surface layer acting as a generic neutral hydrophilic polymer entirely outside the membrane, with its effect explained through steric interactions, is not sufficient. The phenomena we have observed may affect both the interaction between the liposome and bloodstream proteins and the liquid-crystalline-gel transition and is thus relevant to nanotechnological drug delivery device design.
我们将 Langmuir 单层膜实验和双层的全原子分子动力学 (MD) 模拟相结合，研究了 PEG 化脂质体的表面结构及其与生理条件下离子环境的相互作用。我们的研究使用了既能形成凝胶相又能形成液晶相的脂质。通过改变 Langmuir 膜实验中的盐浓度，并在模拟中包含生理水平的盐，我们研究了存在于血浆中的盐离子对聚（乙二醇）(PEG) 层结构的影响。我们还研究了 PEG 层与液晶态和凝胶态脂质双层之间的相互作用。MD 模拟得出了两个明确的结果：(a) Na(+) 离子与 PEG 氧原子形成紧密相互作用，PEG 链围绕它们形成环；(b) 在液晶膜的情况下，PEG 渗透到膜的脂质核心，但在凝胶膜的更紧密结构中被排斥。Langmuir 单层结果表明盐浓度会影响 PEG 化脂质体系，这些结果可以用与 MD 模拟结果一致的方式来解释。我们得出结论，目前接受的 PEG 表面层作为一种完全在膜外的通用中性亲水聚合物的观点，其通过空间位阻相互作用来解释其效果是不够的。我们观察到的现象可能会影响脂质体与血液蛋白之间的相互作用以及液晶-凝胶转变，因此与纳米技术药物输送装置的设计相关。
