Stratum corneum permeation

Pugh, W.J. Hadgraft, J. Roberts, M.S. Physicochemical determinants of stratum corneum permeation. In Dermal Absorption and Toxicity Assessment Roberts, M.S., Walters, K.A., Eds. Marcel Dekker, Inc. New York, 1998 245-268. 

Pugh, W. J., J. Hadgraft, and M. S. Roberts. 1998. Physicochemical determinants of stratum corneum permeation. In Dermal absorption and toxicity assessment, edited by M. S. Roberts, and K. A. Walters. New York Marcel Dekker, pp. 245-268. 

Emulsion components enter the stratum corneum and other epidermal layers at different rates. Most of the water evaporates, and a residue of emulsifiers, Hpids, and other nonvolatile constituents remains on the skin. Some of these materials and other product ingredients may permeate the skin others remain on the surface. If the blend of nonvolatiles materially reduces the evaporative loss of water from the skin, known as the transepidermal water loss (TEWL), the film is identified as occlusive. AppHcation of a layer of petrolatum to normal skin can reduce the TEWL, which is normally about 4—8 g/(m h), by as much as 50 to 75% for several hours. The evaporated water is to a large extent trapped under the occlusive layer hydrating or moisturizing the dead cells of the stratum corneum. The flexibiHty of isolated stratum corneum is dependent on the presence of water dry stratum corneum is britde and difficult to stretch or bend. Thus, any increase in the water content of skin is beHeved to improve the skin quaHty. 

In addition, data obtained from infrared, thermal, and fluorescence spectroscopic studies of the outermost layer of skin, stratum corneum (SC), and its components imply enhancer-improved permeation of solutes through the SC is associated with alterations involving the hydrocarbon chains of the SC lipid components. Data obtained from electron microscopy and x-ray diffraction reveals that the disordering of the lamellar packing is also an important mechanism for increased permeation of drugs induced by penetration enhancers (for a recent review, see Ref. 206). 

The skin is composed of an outer layer called the stratum corneum. This layer consists of dead, dried cells that are resistant to permeation by toxicants. Absorption also occurs through... 

Originating from the structure of the stratum corneum, two permeation pathways are possible (a) the intercellular route and (b) the transcellular route. 

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... 

For parallel permeation pathways within a single layer of such a laminate, the total permeability may be calculated as the sum of the permeabilities [49], For example, when assuming that permeation may occur through both a lipid fraction and a protein fraction of the stratum corneum, the total permeability is calculated according to Eq. 34 ... 

In the revised Robinson model, the skin was modeled as a two-layer laminate consisting of stratum corneum and a watery epidermal layer. Permeation through the stratum corneum was assumed to occur through two different pathways [8] ... 

Johnson ME, Blankschtein D, Langer R (1997) Evaluation of solute permeation through the stratum corneum lateral bilayer diffusion as the primary transport mechanism. J Pharm Sci 86 1162-1172. 

Mitragotri S (2002) A theoretical analysis of permeation of small hydrophobic solutes across the stratum corneum based on scaled particle theory. J Pharm Sci 91 744-752. 

Due to the relative ease of oxidation of the parent compound, common delivery forms in cosmetic formulations and clinical trials are vitamin E acetate (a-TAc, structure in Fig. 15.7a) and vitamin E phosphate. These forms are expected to permeate and to regenerate free active a-TH through enzyme-catalyzed hydrolysis activities in skin. Although a-TAc is readily hydrolyzed by esterase action to vitamin E upon oral ingestion, no consensus as to the extent of bioconversion of topically applied a-TAc has been reached. Two published studies demonstrate bioconversion up to 10-15% in the viable epidermis [35] including the basal layer [36]. These and other studies show no detectable metabolism of a-TAc in stratum corneum [37]. 

To distinguish the SC from the underlying epidermis and hence to define the site within the skin to which the a-TAc had permeated, a confocal Raman image was acquired from an untreated section taken from the same piece of skin whose spatial distribution of factor scores is depicted in Fig. 15.3c. A comparison of Fig. 15.3c (factors 1 (SC) and 4 (epidermis)) with the map of a-TAc permeation (Fig. 15.8) clearly reveals that a-TAc remains localized mostly in the stratum corneum, with little reaching the viable epidermis. The... 

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. 

When investigating the effects of water on transdermal permeation, animal skin may yield results markedly different to human data. For example, hairless mouse skin is unsuitable for modeling human stratum corneum regarding hydration effects the murine skin, when hydrated for 24 h, became grossly more permeable than human skin membranes [8]. Thus water effects on skin permeability obtained using animal models need cautious assessment. 

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. 

Hofland et al. investigated the in vitro permeation behavior of estradiol from niosomes (rt-alkyl polyoxyethylenes/cholesterol) through human stratum corneum. In this study examining drug delivery from multilamellar niosomes, small unilamellar niosomes and a micellar solution, all being saturated systems containing 1.5, 1.5, and 0.75 mM estradiol, very low permeation fluxes were detected (64+17, 45 + 15, and 42 + 2 ng/cm2/h, respectively) [40]. 

FIGURE 13.6 Proposed mechanism for permeation of molecules from ethosomal system through stratum corneum (SC) lipids. (Reproduced from Touitou, E. et al., J. Control. Release, 65, 403, 2000. With permission from Elsevier.)... 

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