Molecular Dynamics Simulations Reveal Membrane Interactions for Poorly Water-Soluble Drugs: Impact of Bile Solubilization and Drug Aggregation

Molecular transport mechanisms of poorly soluble hydrophobic drug compounds to lipid membranes were investigated using molecular dynamics (MD) simulations. The model compound danazol was used investigate the mechanism(s) by which bile micelles delivered it membrane. interactions between membrane and pure aggregates—in form amorphous aggregates nanocrystals—were also studied. Our simulations indicate that formed in intestinal fluid may facilitate incorporation into cellular through two different mechanisms. micelle be acting as: i) a shuttle presents directly or ii) an elevator moves solubilized with as colloidal structure itself becomes incorporated within hypothesis supported complementary monolayer adsorption experiments. In these experiments, structures simulated observed rapidly incorporate monolayer. Simulations interaction showed both crystalline nanostructures However, more quickly than nanocrystals membrane, thereby improving absorption.