Getting together without water: Lipid self-assembly in polar non-aqueous solvents

Self-assembled structures have numerous applications including drug delivery, solubilization, and food science. However, to date investigations into self-assembled structures have been largely limited to water, with some additives. This limits the types of assemblies that can form, as well as the accessible temperature range. Non-aqueous, polar solvents such as ionic liquids and deep eutectic solvents offer alternative self-assembly media that can overcome many of these challenges. These novel solvents can be designed to support specific types of assemblies or to remain stable under more extreme conditions. This review highlights recent advances in the field of self-assembly in polar non-aqueous solvents. Here we quantify the contribution of certain solvent properties such as nanostructure and solvent cohesion to lipid self-assembly. While this field is still relatively new, preliminary design rules are emerging, such as increasing hydrophobic regions leading to decreasing solvent cohesion, with a consequent reduction in lipid phase diversity. Ultimately, this review demonstrates the capacity for solvent control of lipid assemblies while also drawing attention to areas that need further work. With more systematic studies, solvents could be explicitly designed to achieve specific lipid assemblies for use in target applications, such as cargo delivery to particular cell types (e.g. cancerous), or triggered release under desired conditions (e.g. pH for release on wound infection).