Abstract
The intercellular lipid matrix of the stratum corneum (SC), which consist mainly of ceramides (CERs), free fatty acids and cholesterol, is fundamental to the skin barrier function. These lipids assemble into two lamellar phases, known as the long and short periodicity phases (LPP and SPP respectively). The LPP is unique in the SC and is considered important for the skin barrier function. Alterations in CER composition, as well as impaired skin barrier function, are commonly observed in diseased skin, yet the understanding of this relationship remains insufficient. In this study, we have investigated the influence of non-hydroxy and α-hydroxy sphingosine-based CERs and their phytosphingosine counterparts on the permeability and lipid organization of model membranes, which were adjusted in composition to enhance formation of the LPP. The permeability was compared by diffusion studies using ethyl-p-aminobenzoate as a model drug, and the lipid organization was characterized by X-ray diffraction and infrared spectroscopy. Both the sphingosine- and phytosphingosine-based CER models formed the LPP, while the latter exhibited a longer LPP repeat distance. The ethyl-p-aminobenzoate flux across the sphingosine-based CER models was higher when compared to the phytosphingosine counterparts, contrary to the fact that the α-hydroxy phytosphingosine-based CER model had the lowest chain packing density. The unanticipated low permeability of the α-hydroxy phytosphingosine-based model is probably associated with a stronger headgroup hydrogen bonding network. Our findings indicate that the increased level of sphingosine-based CERs at the expense of phytosphingosine-based CERs, as observed in the diseased skin, may contribute to the barrier function impairment.
Highlights
The skin is a large multilayered organ with the primary function of protecting the body from an influx of dust, pathogens, chemicals, ultraviolet radiation and other unwanted substances in the external environment, while preventing the excessive loss of fluids from the body [1]
E-PABA was analyzed by means of the Ultra high performance liquid chromatography (UPLC) method
Our results demonstrate that membranes containing CERs with the phytosphingosine subclass exhibited a stronger lipid barrier
Summary
The skin is a large multilayered organ with the primary function of protecting the body from an influx of dust, pathogens, chemicals, ultraviolet radiation and other unwanted substances in the external environment, while preventing the excessive loss of fluids from the body [1]. The outermost layer of the skin, the stratum corneum (SC), is fundamental to the skin barrier function [2,3]. It consists of keratinfilled dead cells, referred to as corneocytes, embedded in a highly organized lipid matrix [4]. The tortuous intercellular pathway occupied by the lipid matrix is the preferred pathway for exogenous substance penetration through the skin [5,6]. Knowledge of the lipid composition and organization is crucial to understand the skin barrier function
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