Ethanol‐Responsive Nanostructures in Glycerol Monooleate/Triolein Dispersions

Dispersed lipid liquid-crystalline nanoparticles are promising carriers for bioactive compounds in food and pharmaceutical formulations. Ethanol is widely used as a cosolvent and processing aid; however, its direct effect on the internal nanostructure of pre-formed dispersed lipid systems remains poorly understood. Here, we investigate ethanol-induced nanostructural transitions in glycerol monooleate (GMO) and triolein/GMO dispersions using small-angle x-ray scattering, cryogenic transmission electron microscopy, and dynamic light scattering. In GMO dispersions, increasing ethanol content (lipid/ethanol weight ratios from 1/0 to 1/5) induces structural transitions from inverse bicontinuous cubic (Im3m) phases to sponge phases and, at higher ethanol levels, to structures consistent with direct micelles. In TO/GMO dispersions (20/80 to 50/50), ethanol transforms inverse hexagonal or inverse microemulsion-type structures into sponge-type phases, followed by macroscopic phase separation at elevated ethanol contents. In these phase-separated systems, the aqueous phase contains direct micellar aggregates, whereas the lipid-rich phase retains inverse nanostructures or becomes dominated by triolein-rich domains. These findings demonstrate that ethanol acts as a compositional trigger for nanostructural transitions in dispersed lipid systems and provide mechanistic insight into ethanol-lipid interactions, establishing ethanol responsiveness as a design principle for tunable lipid-based delivery systems.