Association of ibuprofen at the polar/apolar interface of lipid membranes

Ibuprofen is a non-steroidal anti-inflammatory drug widely used to treat inflammatory diseases, and for its analgesic and antipyretic activity. Although operating as a protein inhibitor, it is also known to interact with lipid membranes. We combined calorimetry, electron spin resonance, attenuated total reflectance-Fourier transform infrared and molecular docking to characterize the interaction of ibuprofen with dimyristyolphosphatidylcholine (DMPC) bilayers, as a function of temperature and drug concentration. At increasing concentration, ibuprofen first perturbs and then suppresses the DMPC pre-transition, stabilizes the fluid state, and favours gel-fluid phase coexistence. The drug decreases the molecular packing of the polar heads and of the first methylene segments of lipid membranes in the gel phase, whereas it leaves unperturbed the chain flexibility in the liquid-crystalline phase. The action of ibuprofen also leads to a higher degree of hydration of the bilayer polar heads and favours hydrogen bond formation with solvent molecules. The overall results reveal that ibuprofen affects a number of key molecular properties of DMPC bilayers by binding through non-specific interactions at the polar/apolar interface. [Display omitted] •Ibuprofen associates with DMPC bilayers through non-specific interactions.•The energetically favoured binding site of ibuprofen is at the DMPC polar/apolar interface.•The drug reduces the packing density in the gel state and favours bilayer hydration.•Ibuprofen stabilizes the fluid state of DMPC bilayers.•The DMPC chain flexibility and conformation in the fluid phase are not perturbed.