A Model Membrane Approach to the Epidermal Permeability Barrier

Abstract

The permeability barrier of mammalian skin is found in unusual intercellular domains in the upper layers of the epidermis, and is composed mainly of three lipid classes: ceramide, cholesterol, and free fatty acid. These are organized as lamellae, but the details of lipid organization are not precisely known. To examine the relationship between lipid composition and phase behavior, aqueous dispersions of bovine brain ceramide, cholesterol, and perdeuterated palmitic acid were examined by 2H NMR and compared to analogous systems in which sphingomyelin replaced ceramide. The sphingomyelin systems give rise as expected to a stable fluid lamellar signal over the temperature range 20-75 degrees C and pH 5.2-7.4, whereas the ceramide dispersions show complex polymorphism as a function of both temperature and pH. Prominent features of the ceramide dispersions containing cholesterol are phase coexistence and the presence of a "solid" phase in which molecular motion is more inhibited than in a classical phospholipid gel phase: T1z measurements indicate that lateral diffusion of the palmitic acid probe effectively does not occur. In the absence of cholesterol, a fluid lamellar signal is not observed, but the appearance of a "solid" signal is also influenced by the pH. In the presence of cholesterol, a fluid lamellar signal is present at 50 degrees C, and the 2H NMR order parameter profile is very similar to that derived from the analogous sphingomyelin dispersions.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiscale Modeling Framework of Transdermal Drug Delivery

“…Comparisons of stratum corneum extracted lipids with dmpc and dmpc-cholesterol bilayer systems have suggested that liquid crystalline phase dmpc-cholesterol bilayers would be a reasonable model of stratum corneum lipids for diffusion coefficients of solute molecules 22,24,31 and is further corroborated by the agreement for the calculated and experimental fentanyl flux. However, the effects of permeation enhancers on dmpc/cholesterol bilayer systems might be different from their effects on stratum corneum lipids, and experimental verification of the degree to which oleic acid increases fentanyl flux is needed.…”

Cutaneous water loss and sphingolipids in the stratum corneum of house sparrows,Passer domesticusL., from desert and mesic environments as determined by reversed phase high-performance liquid chromatography coupled with atmospheric pressure photospray ionization mass spectrometry

“…Lipids within the SC are organized in layers called lamellae, but the details of how individual lipid molecules are involved in the organization of the SC remain obscure (Kitson et al, 1994;Bouwstra et al, 2003;Hill and Wertz, 2003). It is thought that ceramides form the structural backbone of the lamellae, and those containing linoleic acid serve to rivet bilayers together (Bouwstra et al, 2003;Lillywhite, 2006).…”

The physical chemistry of the stratum corneum lipids

“…In the hexagonal (HEX) phase, the all-trans lipid chains have some rotational mobility along their long axes, but their translational mobility is restricted. In the liquid-crystalline (LIQ) phase, the chains have a high degree of gauche isomerization and their lateral organization is completely lost; the chains have both high rotational and high translational mobility in the plane of the membrane.Data from FTIR, WAXD, 2 H NMR and electron diffraction have shown that all three phases are present in healthy human SC, with a notable prevalence of the OR phases [83][84][85][86][87], contrary to an earlier model of a single gel-phase matrix [88]. Thus, the average packing density in the SC lipid lamellae is higher than the one Figure 3 A scheme illustrating the three-dimensional structure of the lipid lamellae.…”