Effect of cholesterol on miscibility and phase behavior in binary mixtureswith synthetic ceramide 2 and octadecanoic acid. Infrared studies

The three main lipid components of the stratum corneum, namely ceramides, f ree fatty acids and cholesterol, play a fundamental role in the maintenance of the skin barrier. The current investigation is aimed toward understandi ng the miscibility and intermolecular interactions of these lipids. Toward this end, Fourier transform infrared spectroscopic studies of the three pos sible equimolar binary mixtures of cholesterol, a synthetic non-hydroxylate d fatty acid N-acyl sphingosine with a C18 chain length (N-stearoylsphingos ine, approximating human ceramide 2), and stearic acid were undertaken. The thermotropic responses of the methylene stretching and scissoring vibratio ns were used to evaluate chain conformation and packing respectively. Selec tive perdeuteration, of either the stearic acid or the ceramide acid chains , permitted separate and simultaneous evaluation of the conformational orde r and packing properties of the sphingosine chain, the amide linked fatty a cid chains and/or the stearic acid chain. Whereas cholesterol mixed well wi th ceramide at physiological temperatures, the stearic acid was miscible wi th the cholesterol only at relatively high temperatures where the fatty aci d is disordered. A complex interaction between stearic acid and ceramide wa s detected. A separate fatty acid-rich phase persisted until at least 50 de greesC, whereas at higher temperatures the components appear to be quite mi scible. However, a preferential association of the fatty acid with the cera mide base chain is indicated. None of the binary systems studied exhibit mi scibility and interactions resembling those in the ternary mixtures of thes e substances, which is widely used to model stratum corneum. The role of ch olesterol in controlling the miscibility characteristics in the ternary sys tem is evident. (C) 2001 Elsevier Science B.V. All rights reserved.