Exploiting salting effects to tune morphology and phase boundaries of lipidic mesophases

Understanding the effects of salts on non-ionic surfactants is crucial for optimizing soft material properties in pharmaceutical, biomedical and materials science applications where precise control of self-assembled structures determines functionality. In this study, the effect of salts and amphiphilic additives on monoolein (MO), one of the most studied lipids for these applications, was investigated using small-angle X-ray scattering (SAXS). The effects of different salts, varying in ionic strength and Hofmeister classification, on the lattice parameter and phase transitions were explored. Chaotropic salts, such as NaI, promoted mesophase hydration and increased the lattice parameter, while kosmotropic salts, such as NaH₂PO₄, reduced the lattice parameter and induced bilayer curvature, similar to the effect of increasing temperature. The introduction of the amphiphilic molecule N-(2,3-Dihydroxypropyl) oleamide (MOA1) into the MO-water system led to swelling of the cubic phase unit cell and, at higher concentrations, a phase transition from Pn3m to Ia3d symmetry. The stability of the cubic phase was strongly dependent on salt type and concentration, with chaotropic salts destabilizing the structure and kosmotropic salts counteracting swelling effects, thereby extending the cubic phase stability range. These interactions can be exploited to fine-tune mesophase properties for enhanced molecular loading, with chaotropic salts facilitating higher incorporation of guest molecules and kosmotropic salts compensating for excessive swelling to maintain mesophase integrity. This study provides insights into the tunability of lipid mesophases for applications in drug delivery, biosensing, and soft material design.