Tuning Nanostructured Lyotropic Liquid Crystalline Mesophases in Lipid Nanoparticles with Protic Ionic Liquids.

We herein report 13 protic ionic liquids (PILs) as tunable solvation media to regulate the internal lyotropic liquid crystalline mesophase of monoolein-based nanoparticles. A range of nanostructures, including inverse bicontinuous cubic, inverse hexagonal, and sponge/lamellar mesophases, were produced and verified by synchrotron small-angle X-ray scattering. Notably, manipulating the cation/anion structures of the PILs can alter the monoolein packing behavior and cause a sequential phase transition (hexagonal → cubic → lamellar) in the nanoparticles. The solvent channels inside the nanoparticles were enlarged up to 40% under certain PIL-water conditions, making these materials prospective for encapsulation of large molecules. Finally, a freeze-drying study demonstrated the ability of PILs to preserve nanostructure upon reconstitution of the nanoparticles compared to that in pure water. This study opens a new route for fine-tuning lyotropic liquid crystalline structures using PILs, which circumvents issues encountered using conventional salts.