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Phase behavior of skin lipid mixtures: the effect of cholesterol on lipid organization

Drug Delivery Technolog

The cornified envelope-bound ceramide fraction is altered in patients with atopic dermatitis

Drug Delivery Technolog

Topically Applied Ceramides Interact with the Stratum Corneum Lipid Matrix in Compromised Ex Vivo Skin

Drug Delivery Technolog

Barrier Capability of Skin Lipid Models: Effect of Ceramides and Free Fatty Acid Composition

-aminobenzoate permeation and transepidermal water loss values as markers for barrier function, we determined that the alterations in SC lipid composition contribute to the impaired barrier function in AD patients. By the use of biophysical techniques, we established that the largest reduction in barrier capability was observed in the model with an increased fraction of short-chain FFAs, evident by the decrease in chain packing density. Modulations in the CER subclass composition impacted the lamellar organization while having a smaller effect on the barrier function. These findings provide evidence that AD therapies normalizing the FFA composition are at least as important as normalizing CER composition.Drug Delivery Technolog

Increased levels of short-chain ceramides modify the lipid organization and reduce the lipid barrier of skin model membranes

The skin barrier function is attributed to the stratum corneum (SC) intercellular lipid matrix, which is composed primarily of ceramides (CERs), free fatty acids, and cholesterol. These lipids are organized in two lamellar phases: the short and long periodicity phases (SPP and LPP), respectively. The LPP is considered important for the skin barrier function. High levels of short-chain CERs are observed in various inflammatory skin diseases and have been correlated with barrier dysfunction. In this research, we investigated how the increase in the fraction of the short-chain CER with a nonhydroxy C16 acyl chain linked to a C18 sphingosine base CER NS(C16) at the expense of the physiological chain length CER NS with a C24 acyl chain (CER NS(C24)) impacts the microstructure and barrier function of a lipid model that mimicked certain characteristics of the SC lipid organization. The permeability and lipid organization of the model membranes were compared with that of a control model without CER NS(C16). The permeability increased significantly when ≥50% of CER NS(C24) was substituted with CER NS(C16). Employing biophysical techniques, we showed that the lipid packing density reduced with an increasing proportion of CER NS(C16). Substitution of 75% of CER NS(C24) by CER NS(C16) resulted in the formation of phase-separated lipid domains and alteration of the LPP structure. Using deuterium-labeled lipids enabled simultaneous characterization of the C24 and C16 acyl chains in the lipid models, providing insight into the mechanisms underlying the reduced skin barrier function in diseased skin.Drug Delivery Technolog

Evidence of hydrocarbon nanodrops in highly ordered stratum corneum model membranes

Drug Delivery Technolog