Novel process for producing cubic liquid crystalline nanoparticles (cubosomes)

A novel process for producing cubic liquid crystalline nanoparticles (cubos omes) has been developed. The process entails simple mixing of two waterlik e solutions with a minimal input of energy. The key to this process is the inclusion of hydrotrope. Most lipids, such as monoolein, used to form cubic liquid crystals are essentially insoluble in water. The hydrotrope dissolv es the lipid to create a waterlike solution. Water is added to the hydrotro pe solution, resulting in a precipitous decrease in lipid solubility. Provi ded that the dilution trajectory falls into a cubic phase-water miscibility gap, nanometer-scale cubic liquid crystalline particles form spontaneously , presumably from a homogeneous nucleation mechanism. The process is versat ile enough to accommodate any lipid and hydrotrope combination that forms c ubic liquid crystalline material upon dilution. Actives and stabilizers can be formulated into either of the two solutions, allowing the production of colloidally stabilized, controlled-release dispersions. The phase diagram of the monoolein-ethanol-water system is determined to assess appropriate f ormulation of solutions and to develop dilution trajectories. This process replaces current processes that require long hold times, processing of soli dlike materials, and very high-energy inputs to create cubosome nanoparticl e dispersions. This process produces smaller, more stable cubosomes than by conventional bulk dispersion techniques.