Barrier properties of skin

Gender, too, affects the appearance of human skin. Nevertheless, there is little evidence that the skin of males and females differs greatly in permeability. However, there are established differences in the barrier properties of skin across the races of humans. While the horny layers of Caucasians and Blacks are of equal thickness, the latter has more cell layers and is measurably denser [30]. As a consequence, black skin tends to be severalfold less permeable [30,31],... 

Figure 35.2. Schematic representation of the barrier property of skin composed of proteinaceous keratinocytes (corneocytes) embedded in an extracellular nonhomogenous matrix of lipid. Arrow depicts intercellular lipid pathway.

Stratum Corneum Structure. Reviewers agree that for most compounds the rate-limiting barrier properties of skin are located within the SC (2, 10, 12, 15, 16, 21), The texture and cohesiveness of this tissue are familiar to anyone who has ever peeled bits of it from sunburned skin large sheets of SC can be separated from skin (2). Such sheets look like used polyethylene film, and their resistance to water diffusion approximates that of Mylar film of similar thickness (16). However, each sheet is a mosaic made of individual cells (2). 

Before the discussion of transdermal transport, it is essential to understand the anatomy and barrier properties of skin. Briefly, the skin can be viewed as two main layers the epidermis and the dermis. The thickness of epidermis varies from approximately 0.07 to 0.12mm (except on the palms and the soles), and is composed of the stratum corneum, stratum lucidum, stratum... 

The barrier properties of skin vary with the species of animal, and within a species may differ between regions of the body. Based on limited data obtained... 

Outside the field of membrane biochemistry, few researchers investigate the interactions of nonionic surfactants with proteins [75]. In general, the nonionic surfactants exhibit little substantivity for skin and hair [76]. However, their effects on the barrier properties of skin are well known and will be discussed later in this chapter. Because of their passivity, nonionic surfactants are key ingredients in many skin care products, especially facial and sensitive -skin products (Table 5). 

Some workers have suggested that the lauryl chain is of intrinsic biological importance in relation to its ability to disrupt lipid bilayers, having the optimal physical properties of lipophilicity and size, but as C12 compounds are also maximally irritant to the skin (28) where simple lipoidal barrier membranes are probably not involved, other factors are no doubt implicated. Dominguez al. (29) have considered Schott s (26) approach to the biological uniqueness of the dodecyl chain, but have postulated that its properties of skin penetration are related to the conformation of the chain, especially when adsorbed to or interacting with protein. Dominguez e postulate that... 

Some evidence indicates that long-term use of topical antimicrobial agents may alter skin flora. Water content, humidity, pH, intracellular lipids, and rates of shedding help retain the protective barrier properties of the skin. When the barrier is compromised (e.g., by hand hygiene practices such as scrubbing), skin dryness, irritation, cracking, and other problems may result. Although the palmar surface of the hand has twice as many cell layers and the cells are >30 times thicker than on the rest of the skin, palms are quite permeable to water. 

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 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. 

Loden, M., Urea-containing moisturizers influence barrier properties of normal skin. Arch. Dermatol. Res., 1996, 288 103-7. 

At first glance it might seem a bizarre idea to improve a normal skin barrier. Can there be a better barrier than the normal barrier However, we know there is considerable individual variation. Marie Loden5 demonstrated that indeed some moisturizers improve barrier properties of normal skin. Sensitive skin is a multidimensional phenomenon but at least in part a weak SC barrier contributes... 

To deliver a therapeutically-effective dose transdermally using a TDD system with a reasonable size (e.g., < 20 cm ), the barrier properties of the skin for drug permeation must be overcome to effectively deliver the drugs transdermally at a controlled rate. The following approaches have been shown to potentially decrease the skin s barrier properties and enhance the transdermal permeation of the drugs (ji) ... 

The reasons, therefore, for the excellent barrier properties of the skin are the tortuous route and that a penetrant has to cross sequentially a large number of rigid bilayers. The role of the lipids in topical delivery, how they control water transfer through the skin, and how biophysical techniques have been used to examine them have been reviewed [18-20]. 

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]. 

The choice of receptor fluid can influence the outcome of the study considerably (Ramsey et al., 1994 Bronaugh, 1995). In order to avoid underestimation of skin absorption, the test compound should be soluble in the receptor fluid. On the other hand, the receptor fluid should not damage the barrier properties of the skin membrane. Various receptor fluids have been used, including saline (for hydrophilic test substances) and water/ethanol mixtures, or saline supplemented with bovine serum albumin or poly(ethylene glycol) 20 oleyl ether (for testing of lipophilic compounds). When performing studies with metabolicaUy active skin preparations, the receptor fluid should support the viability of the skin. In these cases, a tissue culture medium is normally used. 

In the past decade a number of physical techniques have been used to evaluate the unique barrier properties of mammalian skin [1]. This chapter deals with the use of another physical technique, fluorescence spectroscopy, to study the barrier properties of the human stratum corneum (SC), specifically with respect to the transport of ions and water. The SC is the outermost layer of the human epidermis and consists of keratinized epithelial cells (comeo-cytes), physically isolated from one another by extracellular lipids arranged in multiple lamellae [2]. Due to a high diffusive resistance, this extracellular SC lipid matrix is believed to form the major barrier to the transport of ions and water through the human skin [3-5]. The objective of the fluorescence studies described here is to understand how such extraordinary barrier properties are achieved. First the phenomenon of fluorescence is described, followed by an evaluation of the use of anthroyloxy fatty acid fluorescent probes to study the physical properties of solvents and phospholipid membranes. Finally, the technique is applied to the SC to study its diffusional barrier to iodide ions and water. 

An important function of animal skin is to act as a barrier to prevent water loss and entry of foreign materials. In man and other mammals this barrier property is conferred by the outermost layer known as the stratum corneum. Although it is composed essentially of a few layers of cells which undergo extensive keratinization as they are forced upward from the dermis layer, the barrier properties of this stratum corneum layer far exceed those of keratin. The eflBciency of stratum comeum as a barrier depends on the presence in it of lipoidal material. This eflBciency (I) is severely impaired if the stratum corneum is treated with combinations of polar, water miscible liquids such as methanol and water immiscible lipophilic solvents such as hexane or chloroform. 

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