Ceramide analogue 14S24 selectively recovers perturbed human skin barrier

Self Cite

Stratum corneum ceramides are major determinants of skin barrier function. Although their physiological and pathological role has been widely investigated, to date no structure-activity relationships have been established. In this study, a series of short-chain ceramide analogues with polar head structure identical to ceramide NS, a sphingosine length of 12 carbons and an acyl chain length of 2–12 carbons was synthesized. Their effect on skin permeability was evaluated using porcine skin and two model drugs, theophylline and indomethacin, and compared to that of a physiological ceramide NS. The results showed that the ceramide chain length was crucial for their barrier properties. Ceramides with a 4- to 8-carbon acyl chain were able to increase skin permeability for both drugs up to 10.8 times with maximum effect at a 6-carbon acyl chain. No increase in permeability was found for ceramide analogues with 2- and 12-carbon acyl chains and ceramide NS. The same relationships were obtained for skin concentrations of the model drugs. The relationship between ceramide acyl chain length and its ability to perturb skin barrier showed striking similarity to the behavior of short-chain ceramides in sphingomyelin/phospholipid membranes and confirmed that short-chain ceramides do not act as natural ceramides and their use as experimental tools should be cautious.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Short-Chain Ceramides Decrease Skin Barrier Properties

Novotný¹,

Janůšová²,

Novotný³

et al. 2008

Self Cite

“…In another study, the use of CER-containing cream showed a significant improvement of erythema, pruritus and fissuring compared with controls. Hence, there are some commercially available formulations intended for the direct replenishment of SC lipids in the SC, such as Lipobase® Repair Cream (Astellas Pharma Europe, Prague, Czech Republic), which contains CER[NS], CHOL and FFAs and is prescribed to moderate-to-severe dry skin conditions such as AD, irritant and allergic contact dermatitis and chronic hand eczema [96]. Other commercial formulations in the market which contain CERs are CeraVe®, TriCeram®, Atopiclair® and MimyX® Creams.…”

Section: Skin Diseases and Sc Lipid Substitution Therapymentioning

confidence: 99%

“…Vavrova et al [96] investigated the role of a cream containing a CER[NS] analogue, N-tetracosanoyl-( L )-serine tetradecyl ester (fig. 5; formed by replacement of the allylic hydroxyl NS by an ester group), on the barrier function of the skin.…”

Section: Skin Diseases and Sc Lipid Substitution Therapymentioning

confidence: 99%

Skin Diseases Associated with the Depletion of Stratum Corneum Lipids and Stratum Corneum Lipid Substitution Therapy

Sahle

Gebre‐Mariam²,

Dobner³

et al. 2014

171

164

The skin is the largest organ of the body, whose main function is to protect the body against the loss of physiologically important components as well as harmful environmental insults. From the inside to the outside, the skin comprises three major structural layers: the hypodermis, the dermis and the epidermis. The epidermis contains four different sublayers, the stratum corneum (SC), stratum granulosum, stratum spinosum and stratum basale, where the barrier function of the skin mainly lies in the outermost layer of the epidermis, the SC. The SC contains corneocytes that are embedded in a lipid matrix existing in the form of lipid bilayers. The lipid bilayers are formed mainly from ceramides, free fatty acids and cholesterol, constitute the only continuous pathway across the SC and are responsible for the barrier function of the skin. However, the depletion or disturbance of SC lipids in the SC leads to a perturbation of the barrier function of the skin, and, conversely, several skin diseases such as psoriasis and atopic dermatitis are associated with the depletion of these SC lipids. Therefore, it is of paramount importance to understand the interrelationship between the depletion of SC lipids and skin diseases as well as factors that affect the composition and organization of SC lipids in order to assess the potential benefit of a direct replacement of the missing SC lipids as a means of treating affected, aged or diseased skin. i 2014 S. Karger AG, Basel

“…In fact, preliminary studies using topical lipid mixtures containing, among other things, ceramides, pseudoceramides or other lamellar phase-forming lipids have shown favorable results in treating dry skin and atopic dermatitis [67,68,69,70]. …”

Section: Future Directionsmentioning

confidence: 99%

Current Understanding of Skin Biology Pertinent to Skin Penetration: Skin Biochemistry

2013

The purpose of this review is to summarize some of the biochemical or chemical findings that have contributed most significantly to our current understanding of the permeability barrier of the skin. This literature survey covers the period from the 1970s up to the present. This seems appropriate since earlier progress was comprehensively covered in a 1978 review by Bob Scheuplein entitled ‘Permeability of the skin: a review of major concepts' and in the earlier review by Scheuplein and Blank entitled ‘Permeability of the skin'. Both of these review articles are still being cited, and the earlier one has been cited more than 800 times. Overlap with material covered in these earlier publications will be minimized. The overall significance of findings from some of the most recent years may not yet be determined. The emphasis will be placed on the determination of the composition and structures of the epidermal lipids, especially those of the stratum corneum, key enzymes in the biosynthesis of these lipids and some of the physical chemical properties of these lipids as revealed by X-ray diffraction, infrared spectroscopy and other physical methods.