Stratum corneum mechanical properties

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. 

Drugs that are used to treat hyperkeratosis, a thickening of the stratum corneum, are called keratolytics. Examples of these agents are salicylic acid, urea, lactic acid, and colloidal or precipitated sulfur. The precise mechanisms by which these agents treat hyperkeratosis are not known. Presumably, a common property is the ability to denature keratin, the major structural protein of the epidermis. Other beneficial effects vary among the different drugs. All of them have antimicrobial or... 

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. 

The physical state and molecular organization of the stratum corneum intercellular lipid matrix largely determines the hydration-level of the stratum corneum and thus, indirectly, the mechanical properties and appearance of the skin. A better understanding of stratum corneum lipid organization may thus aid the development of more efficient cosmetic formulations. 

A new generation of transdermal drug delivery (TDD) system was developed to contain one or more skin permeation enhancers in the surface adhesive coating layers. This TDD system has been found, experimentally, to release the enhancers to the surface of stratum corneum to modify the skin s barrier properties, prior to the controlled delivery of the active drug. The extent of enhancement in skin permeability appears to be dependent upon the chemical structure of drug to be delivered transdermally as well as the type and the concentration of enhancer used. The mechanism of skin permeation enhancement have been explored and are analyzed in this report. 

Our last example of the mechanical properties of a protein is that of keratin found in the top layer of skin. The stratum corneum in skin is almost exclusively made up of different keratins that have an a-helical structure. The helices do not run continuously along the molecule so the structure is not ideal. However, the stress-strain characteristics are shown in Figure 6.4 and demonstrate that at low moisture content the stress-strain curve for keratins in skin is approximately linear with a UTS of about 1.8 GPa and a modulus of about 120 MPa. These values are between the values reported for elastin and silk, which is consistent with the axial rise per amino acid being 0.15 nm for the a helix. Thus the a helix with an intermediate value of the axial rise per amino acid residue has an intermediate value of the... 

To improve topical therapy, it is advantageous to use formulation additives (penetration enhancers) that will reversibly and safely modulate the barrier properties of the skin. Fick s first law of diffusion shows that two potential mechanisms are possible. The two constants that could be altered significantly are the diffusion coefficient in the stratum corneum and the concentration in the outer regions of the stratum corneum. Thus, one of mechanisms of action of an enhancer is for it to insert itself into the bilayer structures and disrupt the packing of the adjacent lipids, thereby, reducing the microviscosity. The diffusion coefficient of the permeant will increase This effect has been observed using ESR and fluorescence spectroscopy [16,17]. 

Stratum corneum, the nonliving layer of skin, is refractory as a substrate for chemical reactions, hut it has a strong physical affinity for water. The chemical stability of stratum corneum is evident in its mechanical barriers which include insoluble cell membranes, matrix-embedded fibers, specialized junctions between cells, and intercellular cement. The hygroscopic properties of stratum corneum appear to reside in an 80 A-thick mixture of surface-active proteins and lipids that forms concentric hydrophilic interfaces about each fiber. This combination of structural features and surface-active properties can explain how stratum corneum retains body fluids and prevents disruption of living cells by environmental water or chemicals. 

Stratum corneum, the outermost layer of mammalian epidermis, functions physiologically as the principal diflFusion barrier to molecules penetrating the skin and as a protective physical barrier to mechanical insults at the skin surface. Data suggest that these functions are critically dependent on the specific morphological and macromolecular organization of the membrane mosaic (16, 17, 18, 19, 20). Thus, alterations of biophysical properties arise from environmental factors acting directly on the membrane or upon the keratinization process, and they affect... 

Characterization of the keratinized cells by classical histological and biochemical approaches has been difficult because of the intractable nature of the tissue. Yet it is precisely these properties of mechanical strength, insolubility, macromolecular character, and lack of metabolic activity along with its ease of isolation which makes stratum corneum amenable to analysis by physical methods. The extreme complexity of composition, molecular structure, and organization of stratum corneum make interpretation of these macroscopic properties in terms of molecular structure and events dependent heavily on analogous studies of model synthetic polymer systems and the more thoroughly characterized, keratin-containing wool. 

In spite of the fact that stratum corneum cells are metabolically inert, changes in keratin structure and organization occur as each cell transits through the stratum corneum prior to desquamation (28). This suggests some asymmetry in physical and chemical properties through the thickness of the corneum. One demonstration of this is the swelling of fresh frozen transverse sections of corneum in dilute acid or base. The most mature surface cells swell considerably more slowly and to a lesser extent than the lower layers of the corneum (18). Such asymmetry is of particular importance in studying the diflFusion and mechanical properties of this membrane. 

Further demonstration of the influence of water on mechanical properties is shown in Figure 33 where the elastic modulus of stratum corneum is plotted as a function of immersion time in water. The elastic modulus begins to decrease after about a 5-min immersion time corre-... 

X-ray diffraction and IR dichroism studies suggest that the long-range elasticity of wool is related to a reversible molecular transformation of the alpha-keratin to an extended beta form (66). No convincing evidence supports this mechanism in stratum corneum viscoelasticity. In fact, the available evidence suggests that the elastic behavior of corneum is primarily entropic in origin. At low deformations, the mechanical properties of hydrated stratum corneum is best described as the behavior of a lightly-crosslinked rubber. 

Papir, Y., Wildnauer, R., The Mechanical Properties of Stratum Corneum, ... 

Tt is generally recognized that water plays an important role in main-taining skin in a healthy state with desirable mechanical properties (I). This work describes a technique for generating information on the state of water in the stratum corneum in vitro, with particular emphasis on the mobility of water in the corneum matrix and the eflEect of stratum corneum components on the characteristics of water diffusion. The characteristics of water diffusion in the stratum corneum are derived from sorption and desorption kinetics by using a gravimetric technique which allows determination of the amount of water vapor sorbed or desorbed continuously from an air stream of any given relative humidity. 

Permeation of ethanol into the stratum corneum can alter the solubility properties of the tissue with a consequent improvement of drug partitioning into the membrane (Megrab et al., 1995a). A further potential mechanism of... 

Surgical scrub formulations are designed to remove both transient and normal (resident) microorganisms from the hand surfaces [16]. Surgical scrubs, to be effective when used with or without a scrub brush, must demonstrate immediate, persistent, and residual antimicrobial properties and must be low in skin irritation effects when used repeatedly over a prolonged period of time. The product s immediate antimicrobial efficacy is a quantitative measurement of both the mechanical removal and immediate inactivation of microorganisms residing on the skin surface [17]. The persistent antimicrobial effectiveness is a quantitative measurement of its ability to prevent microbial recolonization of the skin surfaces, either by microbial inhibition or by lethality. The residual efficacy is a measurement of the product s cumulative antimicrobial properties after it has been used repeatedly over time. That is, as the antimicrobial product is used over time, it is absorbed into the stratum corneum of the skin and, as a result, prevents microbial recolonization of the skin surfaces. 

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