Effects of Ion Concentration and Headgroup Chemistry on Thin Lipid Film Drainage
Effects of Ion Concentration and Headgroup Chemistry on Thin Lipid Film Drainage
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DOI：
10.1021/acs.langmuir.3c01795
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发表时间：
2023-11-08
期刊：
影响因子：
3.9
通讯作者：
Beltramo，Peter J.
中科院分区：
文献类型：
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作者：
Zabala-Ferrera，Oscar;Beltramo，Peter J.
虽然在过去的几十年里，脂质纳米颗粒在药物递送应用中的应用不断增长，但在药物载体的表征和合理设计方面仍有许多工作要做。传递的一个关键特征是LNP的外部小叶与细胞膜的外部小叶的相互作用，这部分依赖于脂质和离子环境的融合性。在本文中，我们研究了两个脂质单层之间的相互作用，使用薄膜平衡来创建脂质薄膜和干涉测量法来测量薄膜的演变。我们探讨了脂质头基化学和电荷的作用，以及离子溶液条件，在促进或阻碍膜的排水和稳定性。选择特定的头群磷脂酰胆碱（PC）、磷脂酰乙醇胺（PE）、磷脂酰甘油（PG）和磷脂酰丝氨酸（PS）来代表电荷性和融合性的组合。我们在毛细管数范围内量化每个膜的排水特性。定性地说，我们发现随着毛细管数量的增加，薄膜从通过大凹窝的排水转变为通过通道和漩涡的排水。此外，我们观察到阴离子fusogenic （PS）薄膜从低cacl2浓度下的静电主导的膜排水转变为高cacl2浓度下的fusogenic主导的膜排水。了解头基团组成、离子组成和离子浓度的作用将为设计可调囊泡和缓冲系统铺平道路，这些系统在一系列离体和体内环境中表现良好。
While the use of lipid nanoparticles in drug delivery applications has grown over the past few decades, much work remains to be done toward the characterization and rational design of the drug carriers. A key feature of delivery is the interaction of the exterior leaflet of the LNP with the outer leaflet of the cell membrane, which relies in part on the fusogenicity of the lipids and the ionic environment. In this paper, we study the interactions between two lipid monolayers using a thin film balance to create lipid thin films and interferometry to measure film evolution. We probe the role of lipid headgroup chemistry and charge, along with ionic solution conditions, in either promoting or hindering film drainage and stability. Specific headgroups phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and phosphatidylserine (PS) are chosen to represent a combination of charge and fusogenicity. We quantify each film’s drainage characteristics over a range of capillary numbers. Qualitatively, we find that films transition from drainage via a large dimple to drainage via channels and vortices as the capillary number increases. Additionally, we observe a transition from electrostatically dominated film drainage at low CaCl2concentrations to fusogenic-dominated film drainage at higher CaCl2concentrations for anionic fusogenic (PS) films. Understanding the role of headgroup composition, ionic composition, and ionic concentration will pave the way for the design of tunable vesicle and buffer systems that behave desirably across a range of ex vivo and in vivo environments.