Structural modifications of lipid membranes exposed to statins : Langmuir monolayer and PM-IRRAS study

The effects of selected statins on the structure and properties of lipid membranes composed of zwitterionic (1,2- dimyristoyl-sn-glycero-3-phosphocholine, DMPC, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, DMPE) or anionic (1,2-dimyristoyl-sn-glycero-3-phospho-L-serine,DMPS) lipidswere studied for the first time by Langmuir technique combinedwith polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) and Brewster angle microscopy (BAM). The interactions of statins of different hydrophobicity: pravastatin, fluvastatin, and cerivastatin with the polar region of the lipids forming the membrane were monitored by PMIRRAS and the changes of the overallmonolayer structure and organizationwere described on the basis of surface pressure vs. area per molecule measurements and Brewster angle microscopy. Large differences in the action of each of the statins on the lipid monolayers were observed and explained by their different hydrophobicity combinedwith the different degree of hydration of the lipid polar headgroups in themonolayer. Monolayer fluidizing effect was connected with the interaction of statins in the headgroup region of the membrane affecting the original hydrogen bonding in the lipid layers. The most hydrophilic pravastatin interacted only with the polar head groups of the monolayer and affected the organization of the polar part of the lipid membrane by increasing the headgroups hydration. In the case of DMPS, the contribution of electrostatic interactions between the negatively charged headgroups and the drug was observed, and for this lipid especially strong dehydration effect of cerivastatin was revealed. It facilitated the incorporation of the hydrophobic part of the drug into the nonpolar region of theDMPS layer and in this case therewas almost no fluidization of the layer. Strong dehydration effects may be dangerous for the lipid membranes and may also be one of the reasons to avoid cerivastatin in the therapies, despite its known efficacy especially in view of the large doses and prolonged application that are usually needed.