Stratum comeum structure

Harding, C., The stratum comeum structure and function in health and disease. Dermatol. Then 17 6-15, 2004. 

Elias, P. M. et al.. Percutaneous transport in relation to stratum comeum structure and lipid composition. Journal of Investigative Dermatology 76(4) 297-301, 1981. 

Marjukka Suhonen, T., Bouwstra, J,A., and Urtti, A. (1999). Chemical enhancement of percutaneous absorption in relation to stratum comeum structural alterations, J. Controlled Release, 59 149-161. 

Anderson, B. D. and Raykar, P. V., Solute structure-permeability relationships in human stratum comeum, J. Invest. Derm., 1989, 93, 280-286. 

The physical state of the skin is considerable affected by external factors such as relative humidity, temperature, and air movement at the skin surface. If this contact is broken (for example, by external applications of ointments or creams), it is reasonable to assume that the new skin will change in some way, sometimes to an extent that creates new conditions of permeability for the test material. This would be the case, for example, if the stratum comeum becomes more hydrated than normal due to the topical delivery form. Temperature might also have an effect, as is the case when any constituents of the vehicle affect the inner structure of the skin through interactions with endogenous skin substances. Often several of these processes occur together. 

The homy layer consists of about 10% extracellular components such as lipids, proteins, and mucopolysaccharides. Around 5% of the protein and lipids form the cell wall. The majority of the remainder is present in the highly organized cell contents, predominantly as keratin fibers, which are generally assigned an a-helical structure. They are embedded in a sulphur-rich amorphous matrix, enclosed by lipids that probably he perpendicular to the protein axis. Since the stratum comeum is able to take up considerably more water than the amount that corresponds to its volume, it is assumed that this absorbed fluid volume is mainly located in the region of these keratin structures. 

Roberts MS, Pugh WJ, Hadgraft J (1996) Epidermal permeability-penetrant structure relationships 2. The effect of H-bonding groups in penetrants on their diffusion through the stratum comeum. Int J Pharm 132 23-32. 

The most superficial layer of skin is the stratum comeum (SC), which consists of terminally differentiated keratinocytes (comeocytes) that originate from actively proliferating keratinocytes in lower epidermis (basale, spinosum, and granulosum cells), and contain a lamellar lipid layer secreted from lamellar bodies (Fig. 7a). Flydration of the SC is an important determinant of skin appearance and physical properties, and depends on a number of factors including the external humidity, and its structure, lipid/protein composition, barrier properties, and concentration of water-retaining osmolytes (natural moisturizing factors, NMFs) including free amino acids, ions, and other small solutes. 

MacKenzie, I. C. 1969. Ordered structure of the stratum comeum of mammalian skin. Nature 22 881-82. 

FIGURE 12.1 Penetration enhancer activity, (a) Action at intercellular lipids. Some of the ways by which penetration enhancers attack and modify the well-organized intercellular lipid domain of the stratum comeum. (b) Action at desmosomes and protein structures. Such dramatic disruption by enhancers (particularly potent solvents) as they split the stratum corneum into additional squames and individual cells would be clinically unacceptable, (c) Action within comeocytes. Swelling, further keratin denaturation and vacuolation within individual horny layer cells would not be so drastic but would usually be cosmetically challenging (see Menon and Lee [69] for further details). (Reproduced from Barry, B.W., Nat. Biotechnol. 22, 165, 2004. With permission.)... 

Van Hal, D.A., et al. 1996. Structure of fully hydrated human stratum comeum A freeze fracture electron microscopy study. J Invest Dermatol 106 89. 

The barrier properties of human skin have long been an area of multidisciplinary research. Skin is one of the most difficult biological barriers to penetrate and traverse, primarily due to the presence of the stratum corneum. The stratum cor-neum is composed of comeocytes laid in a brick-and-mortar arrangement with layers of lipid. The corneocytes are partially dehydrated, anuclear, metabolically active cells completely filled with bundles of keratin with a thick and insoluble envelope replacing the cell membrane [29]. The primary lipids in the stratum corneum are ceramides, free sterols, free fatty acids and triglycerides [30], which form lamellar lipid sheets between the corneocytes. These unique structural features of the stratum comeum provide an excellent barrier to the penetration of most molecules, particularly large, hydrophilic molecules such as ASOs. 

Norlen, L.P.O. and Al-Amoudi, A. (2004) Stratum comeum keratin structure, function and formation — the cubic rod-packing and membrane templating model. J. Invest Dermatol. 123(4) 715-732. 

Figure 8.1 Schematic structure of the skin, highlighting the dermis, the epidermis and the stratum comeum (outermost layer of the epidermis)...

The stratum comeum is usefully thought of as a brick wall , with the fully differentiated comeocytes comprising the bricks , embedded in the mortar created by the intercellular lipids. A layer of lipid covalently bound to the comified envelope of the comeocyte contributes to this exquisite organization. The intercellular lipids of the stratum comeum include no phosphohpids, comprising an approximately equimolar mixture of ceramides, cholesterol and free fatty acids. These non-polar and somewhat rigid components of the stratum comeum s cement play a critical role in barrier function. On average, there are about 20 cell layers in the stratum comeum, each of which is about 0.5 fim in thickness. Yet, the architecture of the membrane is such that this very thin structure limits, under normal conditions, the passive loss of water across the entire skin surface to only about 250 mL per day, a volume easily replaced in order to maintain homeostasis. 

The epidermis consists of five principal layers and is an area of both intense biochemical activity and differentiation. These layers are the stratum comeum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. The stratum corneum (horny layer) is the uppermost layer of the epidermis and the skin. The stratum corneum is composed of dead keratinocytes, which are called corneocytes, and has an abundance of keratin and lipid structures [8], The stratum comeum is considered the rate-limiting barrier for the diffusion of chemical compounds across the skin. The stratum lucidum (clear layer) is composed of two to three layers of dead flattened keratinocytes which appear translucent under a microscope and are present only in thick glabrous skin. 

Bouwstra, J., Gooris, G., van der Spek, J. and Bras, J. Structural investigations of human stratum comeum by small angle x-ray scattering. J. Invest. Derm. 97 1005-1012, 1991. 

Hou, S., Mitra, A., White, S., Menon, G., Ghadially, R. and Elias, P. Membrane structure in normal and essential fatty acid-deficient stratum comeum Characterization by ruthenium tetroxide staining and x-ray diffration. J. Invest. Derm. 56 215-223, 1991. 

The primary goal of this chapter is to review comprehensively the x-ray diffraction literature concerned with normal, diseased, and penetration-enhancer-treated skin. Because diffraction methods have not been widely utilized in SC structural studies until rather recently, we begin the chapter with a review of the basic principles of diffraction not only as an aid to the reader but also to encourage others to consider the possibility of using x-ray diffraction as means of studying the stratum comeum and its lipids. 

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