Effects of Ion Concentration and Headgroup Chemistry on Thin Lipid Film Drainage

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 CaCl₂ concentrations to fusogenic-dominated film drainage at higher CaCl₂ concentrations 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.