Molecular Dynamics Simulations of Glycocholate−Oleic Acid Mixed Micelle Assembly

We have applied a molecular dynamics (MD) method to investigate the aggregation behavior and physicochemical properties of bile salt as well as bile salt/fatty acid mixed micelles. Local atomic density profiles from the center of the micelles confirm that the self-assembly of the trihydroxy bile salt, glycocholate, is largely driven by hydrophobic aggregation of the nonpolar beta-faces of the steroid backbones. Additional association occurs between neighboring monomers through hydrogen-bonding interactions. The average micellar aggregation number for glycocholate at 37 degrees C with a background salt concentration of 150 mM is shown to be 8.5 molecules per micelle, while the critical micelle concentration (cmc) is 3.1 mM. The good agreement of these results with experimental values illustrates that a MD approach is useful to study mixed micelles of bile salts and fatty acids, critical to the understanding of oral lipid-based formulations. The aggregation behavior and colloidal structure of such micelles are simulated and presented in this article.