New Aspects of the Skin Barrier Organization

Bouwstra, Joke A.; Pilgram, Gonneke S. K.; Gooris, Gert S.; Koerten, Henk K.; Ponec, M.

doi:10.1159/000056391

Cited by 132 publications

(90 citation statements)

References 15 publications

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“…It has been generally interpreted assuming a two-period organization, the largest one at around 11nm to 13.5 nm corresponding to the stacking of a few asymmetric lipid sublayers that are likely to be responsible for the other periods ( ‫ف‬ 4.5 nm and ‫ف‬ 6 nm) observed by SAXS ( 5,(11)(12)(13). For example, these data can be explained readily by a model of molecular lipid arrangement proposed recently by Iwai et al ( 5 ).…”

Section: Waxs Patternsmentioning

confidence: 98%

“…Some authors have in fact proposed that the strength of the 4.5 nm scattering peak of SC is linked to the content of the acylceramide EOH ( 7 ). A number of other models of lipid organization also have been proposed earlier to explain scattering patterns (11)(12)(13)(14)(15). The main focus of this study is to follow possible variations in scattering profi les as a function of the microscopic location within the SC.…”

Section: Lipid Structural Variations Across the Scmentioning

confidence: 99%

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Micron-scale assessment of molecular lipid organization in human stratum corneum using microprobe X-ray diffraction

Doucet

Potter

Baltenneck

et al. 2014

Journal of Lipid Research

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This article is available online at http://www.jlr.org complex and specifi c architecture of the inter-corneocyte lipid matrix ( 2 ) composed of a mixture of ceramides, cholesterol, and long-chain fatty acids. Ultrastructural studies, using electron microscopy and diffraction techniques, have revealed that these lipids are organized in stacked bilayers that are predominantly parallel to the skin surface ( 3-5 ). Part of the lipids is covalently bound to the corneocytes whereas another part represents the "free lipids" removable by solvent extraction.X-ray diffraction is an excellent technique for studying the spatial organization of the intercellular matrix because the lipid molecules are highly ordered and oriented in a crystalline structure. This technique has provided a number of important results with regard to the SC structure. In particular, small-angle X-ray scattering (SAXS) gives information on the inter-bilayer distance in the multi-lamellar lipid structures, whereas the wide-angle X-ray scattering (WAXS) data contain information about the in-plane crystalline arrangement of lipids (lattice type).Most of the SAXS studies of human SC fi nd refl ections corresponding to ‫ف‬ 4.5 nm and ‫ف‬ 6.5 nm inter-bilayer spacings ( 4, 6, 7 ). Some studies have also detected a refl ection corresponding to a spacing of 11-13.5 nm ( 6, 8 ), referred to as the "long periodicity phase" ( 6 ). These data indicate that the SC lipid matrix has a complex organization into multiple sublayers or even phase-separated domains with different lamellar repeat distances.Similar complexity is found at the molecular level using WAXS, where two sets of peaks are found, corresponding to orthorhombic (peaks at 0.41 and 0.37 nm) and hexagonal (peak at 0.41 nm) packing of the lipid chains. In addition, a fraction of lipids might exist in a fl uid or amorphous state, which would then contribute to the broad band corresponding to an average distance of 0.46 nm. Abstract Lipid and protein components of the stratum corneum (SC) are organized in complex supramolecular arrangements. Exploring spatial relations between various possible substructures is important for understanding the barrier function of this uppermost layer of epidermis. Here, we report the fi rst study where micro-focus X-ray scattering was used for assessing fi ne structural variations of the human skin barrier with micrometer resolution. We found that the scattering profi les were unchanged when scanning in the direction parallel to the SC surface. Furthermore, small-angle scattering profi les did not change as a function of depth in the SC, confi rming that the lipid lamellar spacings remained the same throughout the SC. However, the wide-angle scattering data showed that the orthorhombic phase was more abundant in the middle layers of the SC, whereas the hexagonal phase dominated in the surface layers both at the external and the lowest part of the SC; i.e., the lipids were most tightly packed in the middle region of the SC. Taken together, our results demonstrate that micro...

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Section: Waxs Patternsmentioning

confidence: 98%

Section: Lipid Structural Variations Across the Scmentioning

confidence: 99%

Micron-scale assessment of molecular lipid organization in human stratum corneum using microprobe X-ray diffraction

Doucet

Potter

Baltenneck

et al. 2014

Journal of Lipid Research

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“…A topically therapeutic agent is able to penetrate through the skin via the stratum corneum 4 and skin appendages including hair follicle 5 . The stratum corneum route can be divided into transcellular and intercellular routes.…”

Section: Figure 1: Structure Of Skinmentioning

confidence: 99%

DETERMINATION OF PERMEATION PATHWAY OF GENTAMICIN INTO PIGâ€™S EAR SKIN

Fadli¹,

Jiyauddin²,

J³

et al. 2015

Int. Res. J. Pharm.

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Extensive research has been conducted in the recent years with a focus on drug administration via the skin for both topical and systemic drug delivery. Understanding the drug permeation through the skin is crucial for the development of an optimal product. In this study, the permeation of gentamicin through the pig's ear was evaluated. Both plugged and non-plugged skin was used. In non-plugged skin, the hair follicle orifices were open and a significant amount of gentamicin was detected. However, plugged skin, in which hair follicle orifices were artificially blocked, gentamicin can only penetrate to a less extent through interfollicular epidermis and possible through sweat glands. The study was performed using a Franz-type diffusion cell for 24 hours. The samples were withdrawn for each time interval and were analyzed by UV spectrophotometer. Cumulative amount of permeated gentamicin was compared using the drug concentration. The difference in the percentage of drug permeated through plugged and non-plugged was 44.8 %. Based on the obtained results, it can be concluded that the follicular route is an important route for the drug delivery through the skin.

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“…The 9 classes of adult human ceramides are represented in fi gure 5 . The ceramides together with the other SC lipids form a solid tightly packed crystalline phase called an orthorhombic packing state which is the most tightly packed lipid state and provides optimal barrier function [27] . However, just slowing down the rate of water lost through the tissue is not suffi cient, and retention of water is critical for SC functioning.…”

Section: Sc Barrier and Water Retention Capacitymentioning

confidence: 99%

Dry Skin: Environmental Aspects

Rawlings¹

2004

Exog Dermatol

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Water is absolutely essential for the normal functioning of the skin and especially the stratum corneum (SC). However, as the SC is continuously exposed to varying humidities, maintenance of water within the tissue is crucial. Under most circumstances water present within the SC will be derived from bodily water, being lost by transepidermal water loss, and is normally bound by proteins together with naturally occurring hygroscopic compounds found largely within, but also external to, the corneocytes. Small amounts of water escape through this slightly leaky barrier to hydrate the dehydrated outer layers of the SC, and this is key to maintaining SC flexibility, SC maturation and SC desquamation. The retention of water in the SC is dependent on three major mechanisms: (a) the intercellular lamellar lipids whose physical conformation, predominantly an orthorhombic gel phase, provides a tight and effective barrier to the passage of water through the tissue, (b) the presence of corneodesmosome-bound and ceramide-hydrophobed corneocytes which influence the tortuosity of the SC and thereby the diffusion path length of water and (c) the presence of both intracellular and extracellular SC natural moisturizing factors (NMF). The structure, biochemistry and function of the SC and the epidermis can however be disturbed upon environmental challenge, particularly by disruption of the SC barrier resulting in the precipitation of dry flaky skin conditions. The maintenance of barrier function and thereby SC hydration is central to the production and optimal functioning of the SC. Fluctuating atmospheric conditions (high and low dew points) influence the formation of the epidermal barrier lipids, NMF, corneocyte envelope phenotypes and the desquamatory enzymes and are thus an initiator of dry skin. At low atmospheric dew points, the reduced SC water content precipitates the dry skin phenotype. On perturbation of barrier function, a cycle of events begins initially with the superficial dehydration of the SC (leaking of extracellular lipids, disruption of lipid lamellar architecture, loss of water-soluble NMF), the release of inflammatory mediators, induction of hyperproliferation of epidermal keratinocytes resulting in disturbed epidermal differentiation leading to an inferior SC (enhanced production of sphingosine-containing ceramides relative to phytosphingosine-containing ceramides and reduced transglutaminase activity leading to retention of fragile corneocyte envelopes in the superficial layers of the SC that have reduced levels of covalently bound ceramides), together with a flaky skin condition (reduced desquamatory enzyme activities and reduced corneodesmolysis). In extreme cases when inflammation is present, increased levels of proteases are observed in the SC and reduced interleukin 1 (IL-1) levels with increased IL-1 receptor antagonist protein levels. If left untreated, these events will continuously cycle to produce an even poorer skin condition, and ultimately mechanical cracking of corneodesmosomes between the corne...

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New Aspects of the Skin Barrier Organization

Cited by 132 publications

References 15 publications

Micron-scale assessment of molecular lipid organization in human stratum corneum using microprobe X-ray diffraction

Micron-scale assessment of molecular lipid organization in human stratum corneum using microprobe X-ray diffraction

DETERMINATION OF PERMEATION PATHWAY OF GENTAMICIN INTO PIGâ€™S EAR SKIN

Dry Skin: Environmental Aspects

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