Skin barrier

Keratinocyte proliferation is central to the clinical presentation of psoriasis. Keratinocytes are skin cells producing keratin which act as a skin barrier. Increased keratinocyte cell turnover (hyperkeratosis) results in the characteristic thick scaly skin lesions seen in patients with psoriasis.10,11 Hyperkeratosis results from immune derangements. 

One s grasp of topical dosage forms and their functioning can be nicely organized into several broad usage categories. For instance, many products exist to augment the skin barrier (Table 5). Sunscreens and... 

H. Schaefer and T. E. Redelmeier, Skin Barrier— Principles of Percutaneous Absorption, Karger, Basel, 1996, pp. 213-223. 

The pH of intact skin ranges from about 4.8 to 6.0, while interstitial fluid exhibits a pH that is near neutral. The low pH on skin is attributed mainly to the presence of the so-called acid mantle , a natural skin barrier to the external environment [172], Wagner et al. [173] measured both in-vivo and in-vitro pH profiles across human stratum comeum (SC) using the tape stripping technique and a flat surface pH electrode (InLab 426 from Mettler Toledo). They found a steep pH increase from pH 6 to 8 in the first 100 pm after the removal of the SC. 

Strid, J. and Strobel, S., Skin barrier dysfunction and systemic sensitization to allergens through the skin. Curr. Drug Targets Inflamm. Allergy, 4, 531, 2005. 

The chemical incorporated in a vehicle should reach the surface of the skin at a suitable rate and concentration. If the site of action lies in the deeper layers of the epidermis or below, the substance must cross the stratum comeum, if the skin is intact. Both processes, diffusion from the dosage form and diffusion through the skin barriers, are inextricably linked. They should be considered simultaneously and can be influenced by the choice of formulation. 

A. P. M. Lavrijsen, J. A. Bouwstra, G. S. Gooris, A. Weerheim, H. E. Bodde, and M. Ponec. Reduced skin barrier function parallels abnormal stratum comeum lipid organization in patients with lamellar ichthyosis. J. Invest. Dermatol. 105 619-624 (1995). 

J. Bouwstra, G. Pilgram, G. Gooris, H. Koerten, and M. Ponec. New aspects of the skin barrier organization. Skin Pharmacol. Appl. Skin Physiol. 14 52-62 (2001). 

This chapter starts with a short introduction on the skin barrier s properties and the methods employed for analyzing experimental data. This is followed by an overview of several selected approaches to predict steady-state diffusion through the skin. Then a few approaches that approximate the structural complexity of the skin by predicting drug diffusion in biphasic or even multiphasic two-dimensional models will be presented. Finally, the chapter concludes with a short summary of the many variables possibly influencing drug permeation and penetration. 

The success of the Potts-Guy equation led many authors to advocate a single mechanism as the rate determining step for permeation through the skin barrier for all or at least a wide range of solutes diffusion was assumed to occur primarily via the interkeratinocyte lipids of the stratum corneum, a mixture of ceramides, fatty acids, and sterols. While from a macroscopic point of view these lipids may be modeled as a bulk solvent, on a microscopic scale they... 

Despite the success of the comparatively simple models presented so far, they implicitly assume that the skin barrier may be modeled by a homogeneous membrane—which implies that the properties of the barrier do not change with depth and that there exists only a single pathway through the barrier. Obviously, skin is not a homogeneous membrane and therefore in several studies the simple model was extended to include several subsequent skin layers. In addition, possible transport along hair follicles and sweat ducts, for example, was sometimes included. 

Many QSPR models rely on some sort of idealized theoretical model for the transport of a molecule through the skin barrier. The descriptors necessary for predicting skin permeability—usually molecular weight and the octanol-water... 

Usually, a drug is not applied in an aqueous solution but in some sort of formulation (e.g., ointment, powder). The drug interacts with both the formulation and the skin barrier. Similarly, the formulation s ingredients and its manner of application influence the skin s properties (Figure 20.4). 

As mentioned above, a subgroup of patients with atopic dermatitis has a filaggrin loss-of-function mutation Recently, it was shown that filaggrin expression is reduced in atopic dermatitis even in the absence of any mutation [29]. Keratinocytes differentiated in the presence of IL-4 and IL-13 exhibited significantly reduced filaggrin gene expression and neutralization of IL-4 and IL-13 improves skin barrier integrity [30]. This indicates that Th-2 lymphocytes directly contribute to the skin barrier defect in atopic dermatitis. 

For acute smdy data (oral LD50 values compared with inhalation LC50 values), a wide variation was observed for extrapolation from the oral route to the inhalation route suggesting that such an extrapolation is extremely difficult and should not be undertaken. ECETOC also noted that, in most cases, it can be assumed that the dermal route leads to less absorption of a substance than the oral route, because of the skin barrier, and recommended that this should be assessed on a case-by-case basis. 

Notman, R., Anwar, J., Briels, W.J., Noro, M.G., den Otter, W.K. Simulations of skin barrier function free energies of hydrophobic and hydrophilic transmembrane pores in ceramide bilayers. Biophys. J. 2008, 95, 4763-71. 

Surface-active substances, which are known to enhance penetration through the skin barrier, also needs to be added. These should, of course, not cause any irritation in the nose and other air pathways. Insulin is currently being marketed commercially for IDD. 

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. 

The influence of a cream containing 20% glycerin and its vehicle on skin barrier properties has been investigated. Recent studies have shown that polymers offer several advantages and can be used in skin care products. Phase diagrams were determined for lactic and isohexanoic hydroxy acids as well as salicylic acid with water, a nonionic surfactant and a paraffinic oil, to outline the influence of hydroxy acids on the structure in a model for a skin lotion. The results showed the influence of the acid to be similar to that of the oil but that the difference in chain length between the two alpha acids had only insignificant influence. The results are discussed from two aspects the structures involved in the lotion as applied, and the action of the lotion residue on the skin after the evaporation of the water. 

There should be strict personnel protection regimes for all staff handling both the Regumate and treated animals, because the product is known to be able to pass the skin barrier. 

Micali G, Lacarrabba E, Bongu A, West DP (2001) The skin barrier. In Erenkel RK, Woodley DT (eds) The biology of the skin. The Parthenon Publishing Group, London, pp 219-232... 

Vibrational microspectroscopy provides a unique means for molecular level structure characterization of a variety of biological processes associated with skin. For the past several years, this laboratory has utilized Raman and IR spectroscopy, microscopy, and imaging to monitor the biophysics of the skin barrier, mechanisms of drug permeation and metabolism in intact tissue, and, more recently, the complex events that transpire during wound healing in an ex vivo skin model [1-6]. 

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