Templated cocrystallization of cholesterol and phytosterols from microemulsions

Abstract

A major cause of cardiovascular disease is high cholesterol (CH) levels in the blood, a potential solution to which is the intake of phytosterols (PS) known as CH-reducing agents. One mechanism proposed for PS activity is the mutual cocrystallization of CH and PS from dietary mixed micelles (DMM), a process that removes excess CH from the transporting micelles. In this study, microemulsions (MEs) were used both as a model system for cocrystallization mimicking DMM and as a possible alternative pathway, based on the competitive solubilization of CH and PS, to reduce solubilized CH transport levels from the ME. The effects of different CH/PS ratios, aqueous dilution, and lecithin-based MEs on sterol crystallization were studied. The precipitated crystals from the ME-loaded system with PS alone and from that loaded with 1:1 or 1:3 CH/PS mixtures were significantly influenced by ME microstructure and by dilution with aqueous phase (X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) results). No new polymorphic structures were detected apart from the corresponding sterol hydrates. Mixed crystal morphology and the habit of the precipitated sterols were strongly affected by the CH/PS ratio and the structures of the diluted ME. As the amount of PS in the mixture increased or as the ME aqueous dilution proceeded, precipitated crystal shape became more needle-like. The mixed sterols seemed to be forming eutectic solids.