Stratum corneum barrier properties

Methods for Testing Stratum Corneum Barrier Properties... 

Chapter 37 Methods for Testing Stratum Corneum Barrier Properties 475 Ludger Kolbe and Soeren Jaspers... 

It must be stressed that the primary mechanism of many topical irritants (e.g., organic solvents, corrosives) is the impairment to the stratum corneum barrier properties discussed above, reflected by an increase in transepidermal loss (TEWL). If the stratum corneum barrier is perturbed, the feedback response mediated by cytokines (especially TNFa) may be initiated whereby regeneration of the barrier occurs. However, additional responses to these inflammatory mediators may in themselves launch an irritation response mediated by the keratinocytes or lead to an immune reaction if the antigen is recognized. Regardless of the initiating mechanism, the sequelae to many irritants is the same, namely, epidermal cell death. 

Characterization of Stratum Corneum Barrier Properties Using Fluorescence Spectroscopy... 

CJ Graves, C Edwards, R Marks. The effects of protective occlusive gloves on stratum corneum barrier properties. Contact Dermatitis 33 183-187, 1995. 

Skin. The skin s unique molecular transport and barrier properties pose a challenge for transdermal dmg dehvery. Diffusion of dmgs through the stratum corneum, the outer layer primarily responsible for the skin s limited permeabUity, varies by dmg, by skin site, and among individuals. Until recently, virtuaUy aU dmgs appHed to skin were topical treatments. 

T. Kai, T. Isami, Y. Kurosaki, T. Nakayama, and T. Kimura. Keratinized epithelial transport of beta-blocking agents. II. Evaluation of barrier property of stratum corneum by using model lipid systems. Biol. Pharm. Bull. 16 284—287 (1993). 

R. Lange-Lieckfeldt and G. Lee. Use of a model lipid matrix to demonstrate the dependence of the stratum corneum s barrier properties on its internal geometry. J. Control. Release 20 183-194 (1992). 

The skin barrier properties and effect of hand hygiene practices are known to be important in protecting the body. The average adult has a skin area of about 1.75 m2. The superficial part of the skin, the epidermis, has five layers. The stratum corneum, the outermost layer, is composed of flattened dead cells (comeocytes or squames) attached to each other to form a tough, homy layer of keratin mixed with several lipids, which help maintain the hydration, pliability, and barrier effectiveness of the skin. This part of skin has been compared to a wall of bricks (comeocytes) and mortar (lipids) and serves as the primary protective barrier. Approximately 15 layers make up the stratum corneum, which is completely replaced every 2 weeks a new layer is formed almost daily. From healthy skin, approximately 107 particles are disseminated into the air each day, and 10% of these skin squames contain viable bacteria. This is a source of major dirt inside the house and contributes to many interactions. 

Microscopically, the skin is a multilayered organ composed of many histological layers. It is generally subdivided into three layers the epidermis, the dermis, and the hypodermis [1]. The uppermost nonviable layer of the epidermis, the stratum corneum, has been demonstrated to constitute the principal barrier to percutaneous penetration [2,3]. The excellent barrier properties of the stratum corneum can be ascribed to its unique structure and composition. The viable epidermis is situated beneath the stratum corneum and responsible for the generation of the stratum corneum. The dermis is directly adjacent to the epidermis and composed of a matrix of connective tissue, which renders the skin its elasticity and resistance to deformation. The blood vessels that are present in the dermis provide the skin with nutrients and oxygen [1]. The hypodermis or subcutaneous fat tissue is the lowermost layer of the skin. It supports the dermis and epidermis and provides thermal isolation and mechanical protection of the body. 

Compounds that penetrate the stratum corneum via the transepidermal route may follow a transcellular (or intracellular) or intercellular pathway (see Figure 11.1). Because of the highly impermeable character of the cornified envelope (see previous section), the tortuous intercellular pathway has been suggested to be the route of preference for most drug molecules [32], This is confirmed by several microscopic transport studies, in which compounds have been visualized in the intercellular space of the stratum corneum [33-35]. Moreover, it has been demonstrated that drug permeation across stratum corneum increases many folds after lipid extraction [36], Hence, knowledge of the structure and physical properties of the intercellular lipids is crucial to broaden our insight into the skin barrier function. 

Urea is a hydrating agent (a hydrotrope) used to treat scaling conditions such as psoriasis, ichthyosis, and other hyperkeratotic skin conditions. Applied in a water-in-oil vehicle, urea alone or in combination with ammonium lactate hydrated stratum corneum and improved barrier function when compared to the vehicle alone in human volunteers in vivo [45], Urea also has keratolytic properties, usually when combined with salicylic acid for keratolysis. The somewhat modest penetration-enhancing activity of urea probably arises from a combination of increasing stratum corneum water content (water is a valuable penetration enhancer) and through the keratolytic activity. 

Vavrova, K. 2003. Modification of the skin barrier properties. Penetration enhancers and the stratum corneum repair. PhD diss., Charles University in Prague. 

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. 

Chemical PEs have recently been studied for increasing transdermal delivery of ASOs or other polar macromolecules [35]. Chemically induced transdermal penetration results from a transient reduction in the barrier properties of the stratum corneum. The reduction may be attributed to a variety of factors such as the opening of intercellular junctions due to hydration [36], solubilization of the stratum corneum [37, 38], or increased lipid bilayer fluidization [39, 40]. Combining various surfactants and co-solvents can be used to achieve skin penetration, purportedly resulting in therapeutically relevant concentrations of ASO in the viable epidermis and dermis [41]. In summary, it appears feasible to deliver ASO to the skin using a number of different delivery techniques and formulations. 

Several classes of ceramides have been described in human skin.14 Today it is considered that the ceramides are essential for the barrier properties. It has been suggested that the lower amount of ceramides found in stratum corneum in atopic dermatitis26,27 explains the increased TEWL seen in dry atopic skin. In this context it is of special interest to note that part of the long-chain ceramides of the horny layer are covalently bound to the proteins forming the corneocyte envelope.25 This suggests that such lipids constitute anchors of the hydrophobic phase to the corneocytes and thereby add to the cohesion of the cells of the horny layer. 

Results from in vitro experiments, catalytic properties, and tissue localization are all compatible with the role of SCCE in the degradation of intercellular cohesive structures in the stratum corneum as part of the events leading to remodeling of the tissue and eventually to desquamation. Increased expression of SCCE in the epidermis of transgenic mice leads to impaired barrier function with increased transepidermal water loss. The transgenic animals have a thickened epidermis and a marked hyperkeratosis, possibly reflecting compensatory reactions.47-48 There are also other proteases... 

Golden, G.M., Guzek, D.B., Kennedy, A.H., McKie, J.E., and Potts, R.O. Stratum corneum lipid phase transitions and water barrier properties. Biochemistry. 26 2382-2388 (1987). 

In an own study we tested topical corticosteroids in combination with 5% lanolic acid.68 An improvement of barrier function could be detected. Formulations containing co-3 and co-6 fatty acids may help in the restoration of barrier properties. Higher efficacy of these products may be achieved by combining different classes of stratum corneum lipids 68 Escobar et al.64 showed a clinical improvement of scaling and plaque thickness for topical fish oil compared to the base-treated site in a four week treatment64... 

Bowser, P.A. and White, R.J. Isolation, barrier properties and lipid analysis of stratum compactum a discrete region of the stratum corneum, Br. J. Derm., 112, 1-14, 1985. 

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