Influence of a Novel Dimeric Ceramide Molecule on the Nanostructure and Thermotropic Phase Behavior of a Stratum Corneum Model Mixture

The stratum corneum SC is the outermost layer of the skin and is composed of a multilayered assembly of mostly ceramids Cer , free fatty acids, cholesterol Chol , and cholesterol sulfate Chol S . Because of the tight packing of these lipids, the SC features unique barrier properties defending the skin from environmental influences. Under pathological conditions, where the skin barrier function is compromised, topical application of molecules that rigidify the SC may lead to a restored barrier function. To this end, molecules are required that incorporate into the SC and bring back the original rigidity of the skin barrier. Here, we investigated the influence of a novel dimeric ceramide dim Cer molecule designed to feature a long, rigid hydrocarbon chain ideally suited to forming an orthorhombic lipid phase. The influence of this molecules on the thermotropic phase behavior of a SC mixture consisting of Cer[AP18] 55 wt , cholesterol Chol, 25 wt , steric acid SA, 15 wt , and cholesterol sulfate Chol S, 5 wt was studied using a combination of neutron diffraction and 2H NMR spectroscopy. These methods provide detailed insights into the packing properties of the lipids in the SC model mixture. Dim Cer remains in an all trans state of the membrane spanning lipid chain at all investigated temperatures, but the influence on the phase behavior of the other lipids in the mixture is marginal. Biophysical experiments are complemented by permeability measurements in model membranes and human skin. The latter, however, indicates that dim Cer only partially provides the desired effect on membrane permeability, necessitating further optimization of its structure for medical application