A systematic study of ibuprofen in various lipid bilayers was carried out using molecular dynamics simulation to refine, complements and generalize previously obtained results. Pure bilayers, both saturated and unsaturated, as well as containing 20 and 40 mol % cholesterol were studied at ibuprofen concentrations up to 3% drug/lipid ratio. It was obtained that ibuprofen exhibits similar behavior in all studied bilayers and concentrations. Ibuprofen molecules are located at the region of the lipid heads, forming hydrogen bonds with lipid oxygen and water molecules, and preferably orientated with their hydrophobic parts inside the bilayer. No tendency for clustering of ibuprofen molecules was observed. They are in active motion, rising towards the head region and dipping into the hydrophobic core, and some of them can change their orientation significantly. Ibuprofen does not noticeably affect the properties of the bilayers at the considered concentrations. However, in the bilayer with 40 mol % cholesterol, we found that ibuprofen molecules appeared more often in the center of the bilayer and caused some disorder of the lipid tails.
Shelepova et al. (Wed,) studied this question.