Novel Process for Producing Cubic Liquid Crystalline Nanoparticles (Cubosomes)

Abstract

A novel process for producing cubic liquid crystalline nanoparticles (cubosomes) has been developed. The process entails simple mixing of two waterlike 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 dissolves the lipid to create a waterlike solution. Water is added to the hydrotrope solution, resulting in a precipitous decrease in lipid solubility. Provided 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 versatile enough to accommodate any lipid and hydrotrope combination that forms cubic 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 formulation of solutions and to develop dilution trajectories. This process replaces current processes that require long hold times, processing of solidlike materials, and very high-energy inputs to create cubosome nanoparticle dispersions. This process produces smaller, more stable cubosomes than by conventional bulk dispersion techniques.