Ceramides

Ceramides are the complex lipids consisting of long chain sphingoid base with 16 to 22 carbon molecules (C16-C22), the chain length effects the skin permeability and barrier function of stratum corneum [1]. They are the major constituents of epidermal surface lipids and around twelve different types of ceramides are found in the epidermis which differs from each other only by the hydroxylation reaction or esterification of fatty acids [2, 3]. Among all these types, ceramide 1 plays an essential role in the barrier function on skin cell. 

Ceramides Role in Skin Diseases

There are several skin diseases especially Eczema, Atopic Dermatitis and Psoriasis in which there is a deficiency or disturbance of ceramides. It was summarized in a study [4] that diseases with depletion of lipids can be benefited with the direct lipid replacement therapy. 

While talking about atopic dermatitis, reports suggest that decreases amount and defect in composition of ceramides represents and etiologic factor of the disease, among which Ceramide 1 is most affected in the skin of patients [5]. In addition, Ceramide 3 was also significantly low resulting in an increase in TEWL [6]. This was supported by another report which suggests that ceramide 4 and ceramide 3 were affected significantly in the skin of patients with atopic dermatitis [7]. 

Psoriasis on the other hand is an auto-immune condition of skin in which the proliferation of skin cells in increased by as much as 10 times. This results in development of red bumpy patches with white scales. They are mostly present on elbows and knees. The levels of ceramide 1, 3 and 6 were found to be reduced where as that of ceramide 2 and 5 were elevated. It was concluded in various studies that barrier defect in this disease in part is due to the low levels of ceramide 1 which is the most important class of ceramides in building of waterproof barrier. 

Ceramide Are Helpful in skin Diseases

The traditional (and un-effective) moisturizing creams contain elements such as lanolin or petroleum which serves as a protective coat on the skin which restrict the movement of water in and out of the skin cell [8]. Therefore, these agents can temporarily fix the problem and hydrate the skin which reduces the redness and inflammation of skin [9]. However, they might not address the underlying problem in these disorders and in individuals with sensitive skin they may produce toxic effects; a mentionable flaw is identified in the traditional moisturizers [10]. 

A new advance lipid alternative is used which aim to improve and re-stabilize the waterproof barrier of the skin by the administration of various essential lipid species by topical application, this might help in enhancement of lipid-synthesis capacity. The new generation of moisturizers contains ceramides along with the traditional ingredients which might serve as a barrier repairer. The ceramides used in these formulation are either the synthetic version of ceramide analog present in the skin [11, 12, 13,14] and pseudo-ceramide [15]. Recently, a bio-identical synthetic ceramide (ceramide 1, 3 & 6 ) has been produced which have shown to produce the same action as that of natural ceramides [16].

This is supported by many other reports and studies among which one claims that a multi-lamella system of ceramides , cholesterol  and phytoshingosine play a very important role in reducing the TEWL and subsequently increasing the hydration of skin. Addition of them in a simplified cream may be very beneficial in the improvement of the diseased skin [17]. 

Another study was conducted to observe the effect of various emulsions on barrier repair. An emulsion with ceramide 1 and 9 in a ratio of 0.3 percent, along with cholesterol, 1, 3 butylene glycol and aqueous lecithin were able to revitalize the damaged barrier when observed by TEM imaging. [18]. 

The most recent development in treating atopic dermatitis is the development of triple lipid, ceramide dominant, and barrier repair therapy. This formulation is supported by two clinical studies and is now FDA approved [19]. 

References

  1. Janssens, M.; Van Smeden, J.; Gooris, G.S.; Bras, W.; Portale, G.; Caspers, P.J.; Vreeken, R.J.; Hankemeier, T.; Kezic, S.;Wolterbeek, R.; et al. Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients. J. Lipid Res. 2012, 53, 2755–2766.
  2. Kim, B.E.; Leung, D.Y. Significance of Skin Barrier Dysfunction in Atopic Dermatitis. Allergy Asthma Immunol. Res.2018, 10, 207–215.
  3. Kim, D.H.; Park, W.R.; Kim, J.H.; Cho, E.C.; An, E.J.; Kim, J.W.; Oh, S.G. Fabrication of pseudo-ceramide-based lipid microparticles for recovery of skin barrier function. Colloids Surf. B Biointerfaces 2012, 94, 236–241.
  4. Sahle FF, Gebre-Mariam T, Dobner B, Wohlrab J, Neubert RH: Skin diseases associated with the depletion of stratum corneum lipids and stratum corneum lipid substitution therapy. Skin Pharmacol Phys 2015;28:42–55.
  5. Imokawa G, Abe A, Jin K, Higaki Y, Kawashima M, Hidano A: Decreased level of ceramides in stratum-corneum of atopic-dermatitis – an etiologic factor in atopic dry skin. J Invest Dermatol 1991;96:523–526.
  6. Di Nardo A, Wertz P, Giannetti A, Seidenari S: Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol 1998;78:27–30.
  7. Macheleidt O, Kaiser HW, Sandhoff K: Deficiency of epidermal protein-bound omegahydroxyceramides in atopic dermatitis. J Invest Dermatol 2002;119:166–173.
  8. Elias, P. M., Wakefield, J. S., & Man, M. Q. (2019). Moisturizers versus current and next-generation barrier repair therapy for the management of atopic dermatitis. Skin Pharmacology and Physiology, 32(1), 1-7.
  9. Denda M, Sato J, Tsuchiya T, Elias PM, Fein- gold KR. Low humidity stimulates epidermal DNA synthesis and amplifies the hyperprolif- erative response to barrier disruption: impli- cation for seasonal exacerbations of inflam- matory dermatoses. J Invest Dermatol. 1998 Nov;111(5):873–8.
  10. Li Z, Hu L, Elias PM, Man MQ. Skin care products can aggravate epidermal function: studies in a murine model suggest a patho- genic role in sensitive skin. Contact Dermat. 2018 Feb;78(2):151–8.
  11. Schroter A, Kessner D, Kiselev MA, Hauss T, Dante S, Neubert RH: Basic nanostructure of stratum corneum lipid matrices based on ceramides (EOS) and (AP): a neutron diffraction study. Biophys J 2009;97: 1104–1114.
  12. Kiselev MA, Ryabova NY, Balagurov AM, Dante S, Hauss T, Zbytovska J, Wartewig S, Neubert RH: New insights into the structure and hydration of a stratum corneum lipid model membrane by neutron diffraction. Eur Biophys J 2005;34:1030–1040.
  13. de Jager MW, Gooris GS, Dolbnya IP, Ponec M, Bouwstra JA: Modelling the stratum corneum lipid organisation with synthetic lipid mixtures: the importance of synthetic ceramide composition. Biochim Biophys Acta 2004;1664:132–140.
  14. Sahle FF, Wohlrab J, Neubert RH: Controlled penetration of ceramides into and across the stratum corneum using various types of microemulsions and formulation associated toxicity studies. Eur J Pharm Biopharm 2014;86:244–250.
  15. Uchida Y, Holleran WM, Elias PM: On the effects of topical synthetic pseudoceramides: comparison of possible keratinocyte toxicities provoked by the pseudoceramides, PC104 and BIO391, and natural ceramides. J Dermatol Sci 2008;51:37–43.
  16. Gaur, M.; Dobke, M.; Lunyak, V.V. Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging. Int. J. Mol. Sci. 2017, 18, 208.
  17. Schmitt, T.; Lange, S.; Sonnenberger, S.; Dobner, B.; Demé, B.; Neubert, R.H.; Gooris, G.; Bouwstra, J.A. Determination of the influence of C24 D/(2R)-and L/(2S)-isomers of the CER[AP] on the lamellar structure of stratum corneum model systems using neutron diffraction. Chem. Phys. Lipids 2017, 209, 29–36.
  18. Tessema, E.N.; Gebre-Mariam, T.; Paulos, G.; Wohlrab, J.; Neubert, R.H. Delivery of oat-derived phytoceramides into the stratum corneum of the skin using nanocarriers: Formulation, characterization and in vitro and ex-vivo penetration studies. Eur. J. Pharm. Biopharm. 2018, 127, 260–269.
  19. 56. Tashiro, T.; Nakaune, A.; Kosugi, T.; Arakawa, J.; Mori, H.; Serizawa, S.; Suzuki, K.; Mori, F.; Orikasa, A.; Nakamura, Y. Development of functional cosmetics “ASTALIFT JELLY AQUARYSTA”. Fugifilm Res. Dev. 2011, 56, 1–4.
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