Super-cooled and amorphous lipid-based colloidal dispersions for the delivery of phytosterols

Abstract

Super-cooled and amorphous lipid-based colloids are highly desirable delivery systems because of their ability to encapsulate compounds in a soluble or in a non-crystalline state. In this study, we demonstrate the preparation and characterization of super-cooled and amorphous lipid-based nanoscale colloidal dispersions containing high concentrations of phytosterols (PSs). PSs are highly hydrophobic natural bioactive compounds that are known to significantly reduce blood cholesterol levels in humans, but are insoluble in water and are poorly soluble in common lipids such as triacylglycerols (TAGs). Using the ultrahigh pressure homogenization of pre-heated dispersions, followed by temperature quenching, colloidal dispersions with varying concentrations of PSs in the lipid phase are prepared. Long and medium chain TAGs in combination with a non-ionic surfactant are used. The particle size, morphology and stability are analysed by dynamic and static light scattering, electron microscopy, and X-ray diffraction. Rapid temperature quenching enables the formation of stable colloidal dispersions of 10 wt% PSs, more than five times the equilibrium solubility at room temperature. Super-cooled emulsions are formed using liquid TAG, whereas amorphous particles are formed in the case of solid TAG. In both cases, the complete suppression of the crystallization of both PSs and lipids is observed due to the nanoscale confinement. The colloidal dispersions are stable for at least four months. The insights of this work will help understand the colloid formation and particle morphology control in the development of delivery systems for hydrophobic bio-actives such as drugs, cosmeceuticals, nutraceuticals, nutritional and agricultural nanoscale formulations.