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脂质相在机械应力下对脂质体稳定性的影响。

The effect of lipid phase on liposome stability upon exposure to the mechanical stress.

机构信息

Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wrocław University of Science and Technology, 50-377, Wrocław, pl. Grunwaldzki, 13, Poland.

Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wrocław University of Science and Technology, 50-377, Wrocław, pl. Grunwaldzki, 13, Poland; Lipid Systems sp. z o.o., 54-613 Wrocław, ul. Krzemieniecka 48C, Poland.

出版信息

Biochim Biophys Acta Biomembr. 2020 Sep 1;1862(9):183361. doi: 10.1016/j.bbamem.2020.183361. Epub 2020 May 15.

DOI:10.1016/j.bbamem.2020.183361
PMID:32422137
Abstract

Mechanical properties of a lipid bilayer are parameters determined mainly for giant unilamellar vesicles (GUVs). It is not clear if values obtained on the GUV model can be directly translated to submicron large unilamellar vesicles (LUVs). This ambiguity is a major obstacle in exploring the effect of lipid bilayer mechanics on membrane associated processes and effectiveness of liposome-based targeted drug delivery systems. In presented work extrusion, which is a common method to prepare LUVs, was used to study liposomes preparation and stability upon exposure to mechanical stress. The effect of parameters of the extrusion process (temperature, membrane pore size, extrusion force and volumetric flux) on the properties of liposome suspension (average liposome size, polydispersity index and lipid recovery ratio) was determined for model liposomes composed of DPPC lipid. The state of the DPPC lipid bilayer depends on temperature, therefore, the effect of lipid bilayer mechanics on the extrusion process can be quantitated without altering membrane composition. The extrusion process was carried out with the automated extruder delivering quantitative data on the extrusion force and volumetric flux. Obtained results have been interpreted in terms of mechanical properties of the lipid bilayer. Determined mechanical properties of the lipid bilayer and its dependence on temperature are in good agreement with the literature results determined for GUVs. This shows that mechanical properties of the lipid bilayer does not depend on the liposome size in the range from 100 nm to hundreds of microns.

摘要

脂质双层的力学性质是主要针对巨单层囊泡(GUV)确定的参数。目前尚不清楚在 GUV 模型上获得的值是否可以直接转化为亚微米大单层囊泡(LUV)。这种不明确性是探索脂质双层力学对膜相关过程的影响以及基于脂质体的靶向药物输送系统的有效性的主要障碍。在目前的工作中,挤出是制备 LUV 的常用方法,用于研究在机械应力下暴露时的脂质体的制备和稳定性。确定了由 DPPC 脂质组成的模型脂质体的挤出过程参数(温度、膜孔尺寸、挤出力和体积通量)对脂质体悬浮液的性质(平均脂质体大小、多分散指数和脂质回收比)的影响。DPPC 脂质双层的状态取决于温度,因此,可以在不改变膜组成的情况下定量研究脂质双层力学对挤出过程的影响。挤出过程是使用自动挤出机进行的,该挤出机提供有关挤出力和体积通量的定量数据。根据脂质双层的力学性质对获得的结果进行了解释。确定的脂质双层的力学性质及其对温度的依赖性与 GUV 确定的文献结果非常吻合。这表明,在 100nm 到数百微米的范围内,脂质双层的力学性质不依赖于脂质体的大小。

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