Facile dispersion and control of internal structure in lyotropic liquid crystalline particles by auxiliary solvent...

Submicron sized, structured lyotropic liquid crystalline (LLC) particles, so-called hexosomes and cubosomes, are generally obtained by high energy input dispersion methods, notably ultrasonication and high-pressure emulsification. We present a method to obtain dispersions of such LLC particles with a significantly reduced energy input, by evaporation of an auxiliary volatile solvent immiscible with water, e.g. cyclohexane or limonene. The inner structure of the particles can be precisely controlled by the addition of a nonvolatile oil, such as α-tocopherol or tetradecane consistently with bulk phase diagrams,. Two different lyotropic surfactants were employed, industrial grade monolinoleine (MLO) and soy bean phosphatidylcholine (PC). The lyotropic surfactant and oil phase modifier were first dissolved in the volatile solvent to give a liquid reverse micellar (L2) phase, which requires significantly less energy input to be dispersed in an aqueous solution of secondary emulsifier compared to the corresponding gel-like bulk mesophase. The auxiliary volatile solvent was then removed from the emulsion by evaporation at room temperature, yielding LLC particles of the desired inner structure, Pn3̅m, H2, or Fd3̅m. The obtained particles were characterized by small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and cryogenic transmission electron microscopy (cryo-TEM). Our method enables fine-tuning of the final particle size through the volatile-to-nonvolatile volume ratio and processing conditions.