Emulsions stabilized by phospholipids

Phospholipids are amphiphilic molecules able to adsorb at oil/water interfaces and thus used to stabilize parenteral emulsions. Yet, their low preferred curvature, which sensitively depends on molecular structures and interactions, favors the formation of lamellar phases and sets constraints on the system formulation. Combining phase studies, structural interfacial characterizations, and stability monitoring for different water/phospholipid/oil systems should shine a light on the mechanisms at play and thus tools to optimize formulations. Four phase diagrams were established for ternary aqueous systems containing either DOPC or POPC as the phospholipid and hexadecane or miglyol 812 as the oil. Droplet interfaces were probed using small-angle neutron scattering and the amount of adsorbed lipid was determined using separation and Raman spectroscopy. The metastability of both nano and macro emulsions was systematically assessed over weeks using light scattering. We show that nanoemulsion droplets are stabilized by a lipid monolayer and display excellent metastability if the preferred curvature is positive and large enough, even without any added charges or at high ionic strengths. In contrast, macroemulsion droplets are stabilized with a lipid multilayer, which should possess a positive preferred curvature but also a good enough interfacial anchorage, which is lost upon increasing the preferred curvature. Overall, we provide a rationale for understanding the impact of molecular changes in the formulation on emulsion metastability, through the analysis of the lipid film preferred curvature, layering, and interfacial anchorage.