Skin barrier mechanical

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]. 

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... 

Dermal and transdermal delivery requires efficient penetration of compounds through the skin barrier, the bilayer domains of intercellular lipid matrices, and keratin bundles in the stratum corneum (SC). Lipid vesicular systems are a recognized mode of enhanced delivery of drugs into and through the skin. However, it is noteworthy that not every lipid vesicular system has the adequate characteristics to enhance skin membrane permeation. Specially designed lipid vesicles in contrast to classic liposomal compositions could achieve this goal. This chapter describes the structure, main physicochemical characteristics, and mechanism of action of prominent vesicular carriers in this field and reviews reported data on their enhanced delivery performance. 

Whereas solid microneedle arrays present the opportunity to create conduits through the restrictive skin barrier layer, the application of the formulation into the channel through drycoating the microneedle array or coadministration of a solution, suspension, emulsion, or gel containing the medicament generally relies on passive delivery mechanisms. The capacity to microfabricate hollow microneedles, however, allows a controlled quantity of the medicament to be actively delivered from the tip of the inserted microneedle at a defined rate. In addition, hollow microneedles provide the opportunity to not only deliver substances but also to withdraw material from the skin for analysis, monitoring, and responsive purposes. 

A permeation enhancer can be defined as a compound that alters the skin barrier function so that a desired drug can permeate at a faster rate. Dozens of enhancers are patented each year, and several books have been written summarizing the work and proposing mechanisms of enhancement.70-72 The permeation enhancers may be classified simply as polar and nonpolar ones. They can be used individually or in combination, such as binary mixtures. For several drugs, the flux across skin was observed to be linear with that of the most widely used enhancer, ethanol.73-75 Another polar enhancer, isopropanol, facilitated ion association of charged molecules and enhanced the transport of both neutral and ionic species across the stratum corneum.76 77 While polar enhancers traverse the skin, nonpolar enhancers are largely retained in the stratum corneum both aspects make the combination a superior enhancer to the individual enhancers.78... 

The importance of calcium in the regulation of skin barrier homeostasis is apparent as calcium is involved in the regeneration process of skin barrier components.4 Hence, the balance of calcium level in skin is closely related to hydration of the skin. Apart from the skin, this ion plays a crucial role in various processes in the body, including the growth, death, differentiation, and function of immune cells. The role of calcium in skin is found to be more complex than previously assumed. The elucidation of calcium regulation mechanism in skin could be useful to understand and solve skin problems. 

Tanojo, H. and Maibach, H.I., Role of calcium ions in relation to skin barrier function, in Percutaneous Absorption Drugs-Cosmetics—Mechanisms-Methodology, 3rd ed., Bronaugh, R.L. and Maibach, H.I. Eds., New York, Marcel Dekker 1999, pp. 939-950. 

Histamine receptors are related to skin barrier function.44 Three different types of histamine receptors, HI, H2, and H3 have been reported. First, topical application of histamine HI and H2 receptor antagonists accelerated the barrier repair. Histamine itself, H2 receptor agonist, and histamine releaser delayed the barrier repair. Histamine H3 receptor antagonist and agonist did not affect the barrier recovery rate. Topical application of the HI and H2 receptor antagonists prevented the epidermal hyperplasia induced by barrier disruption under low humidity. The mechanism of the relationship between the histamine receptors and the barrier repair process has not been elucidated yet. 

Certain pitfalls were encountered in the surveillance program whereby elevated PNP levels were observed but did not relate to poor spray techniques. These pitfalls are best illustrated by two case studies. The first was a 28-year-old sprayman, whose persistently elevated PNP levels could not be explained on the basis of a careless technique. It was not until the operator himself was examined and the extensive atopic eczema identified that the cause became apparent. There were deep fissures on the dorsum of his hands and in the interdigital clefts. Later, when his skin condition improved, lower concentrations of urinary PNP were observed, suggesting that the mechanism of this exposure was a breakdown of the natural protection provided by the intact skin barrier. 

The skin barrier can be severely impaired by diseases or mechanical damage. In general, this leads to an increased uptake of compounds via the skin (Wilhelm et al., 1991). Although it may be very well possible that pesticides come into... 

When disruption of the skin barrier occurs, either due to environmental insults, intrinsic constitutional defects, deficient reparative mechanisms or a combination of these factors (Thune 1996a), excessive... 

To keep up its efficiency, the skin barrier has sensitive sensors that detect minor barrier disruptions and induce reparative mechanisms loss of the extracellular... 

There are occupational settings in which dry skin occurs frequently, due to different types of aggression - physical, chemical, mechanical - that separately, concomitantly or sequentially disturb the epidermal skin barrier. However, dry skin does not uniformly affect all workers it occurs mainly in winter and only in more susceptible individuals, namely older ones (Ghadially et al. 1995 Rogers et al. 1996) or those with intrinsic defects in the skin barrier, such as atopies (Imokawa et al. 1991 Elias et al. 1993 Di Nardo et al. 1996 Abeck et al. 1997). 

Fartasch M, Bassukas ID, Diepgen TL (1992) Disturbed extruding mechanism of lamellar bodies in dry non-eczematous skin of atopies. Br J Dermatol 127 221-227 Forslind B (1994) A domain mosaic model of the skin barrier. 

Observable toxic responses in the skin (irritation, allergic reaction) can be directly caused by the presence of surfactant molecules in the dermis, by inflammatory mediators (cytokines) liberated by keratinocytes, or by other substances penetrating the epidermis after the skin barrier function has been impaired by surfactants. The damage of hair fibers is closely related to the impairment of the cuticle layer, which can cause modifications in the mechanical and optical properties of the hair. Substantial differences exist between the mechanisms of skin damage and hair damage, but for the purposes of our discussion, only the common initial event of surfactant-keratin interaction will be considered. 

Skin has also been stored for use as a covering of wounds in bum victims. Preserved skin (allograft) serves as a mechanical and physiological barrier decreases loss of water, protein, and heat and provides strata for the regeneration of viable skin by the victim. The storage medium is usually a tissue culture solution and the skin is wrapped up in gauze that is soaked in this solution and kept for about one week. 

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