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Permeability of the Skin

Robert J. Scheuplein

10.1002/cphy.cp090119

Source: Supplement 26: Handbook of Physiology, Reactions to Environmental Agents

Originally published: 1977

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Manifestations of Skin Permeability
2 Structure of the Skin
2.1 Relevant Structural Features of the Whole Skin
3 The Stratum Corneum
3.1 Regional Variations in Structure
4 Human Versus Other Mammalian Skin
5 Biophysics of Skin Permeability
5.1 Mathematical Analysis of Skin Permeability
5.2 Steady‐State Permeability of Skin—Fick's Law
5.3 Appendageal Diffusion
5.4 Concentration Levels in the Skin
5.5 Regional Variations in Permeability
6 Effect of Solvents and Surfactants
6.1 Water
6.2 Aprotic Solvents
6.3 Surfactants
6.4 Organic Solvents
Figure 1. Figure 1.

Top: stained cross section of human skin. Stratum corneum has porous appearance typical of histological preparations. Bottom: electron photomicrograph of top part of epidermis showing 10 cell layers of stratum corneum.

From Scheuplein & Blank 143
Figure 2. Figure 2.

Schematic of human skin. Dimensions and distances pertain to abdominal skin. The essential elements of the composite skin diffusion barrier are indicated.

From Scheuplein & Blank 143
Figure 3. Figure 3.

Cellular structure of the stratum corneum. A: a fragment of stratum corneum one cell layer thick (phase contrast). Dark bands bordering cells are regions of cell overlap. B: scanning electron photomicrograph of external surface of stratum corneum (washed with carbon tetrachloride prior to gold‐palladium coating.) C: electron photomicrograph of filled intercellular regions in stratum corneum. Adjacent cell boundaries are highly convoluted and interdigitated. D: cross section of stratum corneum showing surprisingly regular vertical stacking of cells. Tissue was swollen in water (pH = 12) and stained with methylene blue.

From Scheuplein & Blank 143. From Scheuplein & Blank 143. Courtesy of A. M. Kligman. Courtesy of A. M. Kligman
Figure 4. Figure 4.

Top: idealized representation of intracellular keratin in stratum corneum. Bottom: electron micrograph of intracellular keratin.

Courtesy of I. Brody
Figure 5. Figure 5.

Quantity of diffusing substance entering (Qin), diffusing through (Qout), and being sorbed (Qm) by a simple membrane. Curves are based on Equations 3,4,5.
Figure 6. Figure 6.

Fick's law plot for aqueous butanol penetrating epidermis.

From Scheuplein & Blank 143
Figure 7. Figure 7.

Permeability data for aqueous alcohol solutions through epidermis. These curves are plotted together to illustrate the validity of the steady‐state permeability relation, Equation 9. Logarithmic plots are used in order to include in a single curve the wide range of data. The exponents are the same for figures 8,9 and 10 in order to facilitate comparison.

From Scheuplein & Blank 144
Figure 8. Figure 8.

Permeability data for the pure liquid alcohols through epidermis as derived from Fick's law, Equation 9. See legend for Figure 7.

From Scheuplein & Blank 144
Figure 9. Figure 9.

Permeability data for aqueous alcohol solutions through dermis as derived from Fick's law, Equation 9. See legend for Figure 7.

From Scheuplein & Blank 144
Figure 10. Figure 10.

Permeability data for the pure liquid alcohols through dermis as derived from Fick's law, Equation 9. See legend for Figure 7.

From Scheuplein & Blank 144
Figure 11. Figure 11.

Effect of solvent (vehicle) on permeability constant of the alcohols.

From Scheuplein & Blank 143
Figure 12. Figure 12.

Free‐energy diagrams for polar (water‐soluble) and nonpolar (lipid‐soluble) molecules diffusing through stratum corneum. Maxima and minima are scaled according to measured values.

From Blank & Scheuplein 27
Figure 13. Figure 13.

Comparison of diffusional resistance of dermis and epidermis for aqueous solutions of alcohols. These resistances were added according to Equation 12 to obtain the total diffusional resistance for the whole skin. R, the diffusional resistance is the reciprocal of the permeability constant.

From Scheuplein & Blank 144
Figure 14. Figure 14.

Approach to steady‐state flow for a membrane with the indicated diffusion constants. (D). Detail near origin (magnified in inset) shows the initial predominance of shunt diffusion.
Figure 15. Figure 15.

The ordinate R = log Qs/QB is the ratio of the shunt to bulk diffusion currents as a function of time. The line R = 0 corresponds to equal currents; the curve above the line corresponds to excess shunt diffusion (Ds), the curves below the line to excess bulk diffusion (DB).

From Scheuplein 140
Figure 16. Figure 16.

Steady‐state and transient concentration levels in the epidermis. The dotted line at 110 μm corresponds to the location of the basal layer of the epidermis; the solid line at 200 μm corresponds to the location of the edge of the papillary plexus. A semi‐infinite approximation was used to obtain the values for the transient cases.

From Scheuplein 140
Figure 17. Figure 17.

Steady‐state concentration profiles for finite, composite skin diffusion barrier. The first number is the diffusion constant in the stratum corneum (δ = 10 μm); the second number is the diffusion constant in the epidermis (δ = 200 μm). The various K values are partition coefficients for the stratum corneum.

From Scheuplein 140
Figure 18. Figure 18.

Approximate transient concentration levels at the site of each type of diffusion shunt at different times (t) after the application of a solution at t = 0. The dotted boundaries represent a concentration level of 10−7 Co, the blackened areas a level of 10−3 Co. (Co is the applied concentration at the surface.) The value of 10−7 corresponds to approximately 10−8 molar when a 1% solution is applied to the skin.

From Scheuplein 140
Figure 19. Figure 19.

Effect of solvents on permeability. Curve shows the increased water permeability of isolated epidermis during treatment with the pure solvents. The low concentration side of the diffusion cell was filled with the solvent, and the tissue was continuously bathed from one side during the experiment.
Figure 20. Figure 20.

Arrhenius curves for the self‐diffusion of water, water diffusion through stratum corneum (lowest curve), and water diffusion through delipidized stratum corneum (middle curve).

From Scheuplein & Blank 144


Figure 1.

Top: stained cross section of human skin. Stratum corneum has porous appearance typical of histological preparations. Bottom: electron photomicrograph of top part of epidermis showing 10 cell layers of stratum corneum.

From Scheuplein & Blank 143


Figure 2.

Schematic of human skin. Dimensions and distances pertain to abdominal skin. The essential elements of the composite skin diffusion barrier are indicated.

From Scheuplein & Blank 143


Figure 3.

Cellular structure of the stratum corneum. A: a fragment of stratum corneum one cell layer thick (phase contrast). Dark bands bordering cells are regions of cell overlap. B: scanning electron photomicrograph of external surface of stratum corneum (washed with carbon tetrachloride prior to gold‐palladium coating.) C: electron photomicrograph of filled intercellular regions in stratum corneum. Adjacent cell boundaries are highly convoluted and interdigitated. D: cross section of stratum corneum showing surprisingly regular vertical stacking of cells. Tissue was swollen in water (pH = 12) and stained with methylene blue.

From Scheuplein & Blank 143. From Scheuplein & Blank 143. Courtesy of A. M. Kligman. Courtesy of A. M. Kligman


Figure 4.

Top: idealized representation of intracellular keratin in stratum corneum. Bottom: electron micrograph of intracellular keratin.

Courtesy of I. Brody


Figure 5.

Quantity of diffusing substance entering (Qin), diffusing through (Qout), and being sorbed (Qm) by a simple membrane. Curves are based on Equations 3,4,5.



Figure 6.

Fick's law plot for aqueous butanol penetrating epidermis.

From Scheuplein & Blank 143


Figure 7.

Permeability data for aqueous alcohol solutions through epidermis. These curves are plotted together to illustrate the validity of the steady‐state permeability relation, Equation 9. Logarithmic plots are used in order to include in a single curve the wide range of data. The exponents are the same for figures 8,9 and 10 in order to facilitate comparison.

From Scheuplein & Blank 144


Figure 8.

Permeability data for the pure liquid alcohols through epidermis as derived from Fick's law, Equation 9. See legend for Figure 7.

From Scheuplein & Blank 144


Figure 9.

Permeability data for aqueous alcohol solutions through dermis as derived from Fick's law, Equation 9. See legend for Figure 7.

From Scheuplein & Blank 144


Figure 10.

Permeability data for the pure liquid alcohols through dermis as derived from Fick's law, Equation 9. See legend for Figure 7.

From Scheuplein & Blank 144


Figure 11.

Effect of solvent (vehicle) on permeability constant of the alcohols.

From Scheuplein & Blank 143


Figure 12.

Free‐energy diagrams for polar (water‐soluble) and nonpolar (lipid‐soluble) molecules diffusing through stratum corneum. Maxima and minima are scaled according to measured values.

From Blank & Scheuplein 27


Figure 13.

Comparison of diffusional resistance of dermis and epidermis for aqueous solutions of alcohols. These resistances were added according to Equation 12 to obtain the total diffusional resistance for the whole skin. R, the diffusional resistance is the reciprocal of the permeability constant.

From Scheuplein & Blank 144


Figure 14.

Approach to steady‐state flow for a membrane with the indicated diffusion constants. (D). Detail near origin (magnified in inset) shows the initial predominance of shunt diffusion.



Figure 15.

The ordinate R = log Qs/QB is the ratio of the shunt to bulk diffusion currents as a function of time. The line R = 0 corresponds to equal currents; the curve above the line corresponds to excess shunt diffusion (Ds), the curves below the line to excess bulk diffusion (DB).

From Scheuplein 140


Figure 16.

Steady‐state and transient concentration levels in the epidermis. The dotted line at 110 μm corresponds to the location of the basal layer of the epidermis; the solid line at 200 μm corresponds to the location of the edge of the papillary plexus. A semi‐infinite approximation was used to obtain the values for the transient cases.

From Scheuplein 140


Figure 17.

Steady‐state concentration profiles for finite, composite skin diffusion barrier. The first number is the diffusion constant in the stratum corneum (δ = 10 μm); the second number is the diffusion constant in the epidermis (δ = 200 μm). The various K values are partition coefficients for the stratum corneum.

From Scheuplein 140


Figure 18.

Approximate transient concentration levels at the site of each type of diffusion shunt at different times (t) after the application of a solution at t = 0. The dotted boundaries represent a concentration level of 10−7 Co, the blackened areas a level of 10−3 Co. (Co is the applied concentration at the surface.) The value of 10−7 corresponds to approximately 10−8 molar when a 1% solution is applied to the skin.

From Scheuplein 140


Figure 19.

Effect of solvents on permeability. Curve shows the increased water permeability of isolated epidermis during treatment with the pure solvents. The low concentration side of the diffusion cell was filled with the solvent, and the tissue was continuously bathed from one side during the experiment.



Figure 20.

Arrhenius curves for the self‐diffusion of water, water diffusion through stratum corneum (lowest curve), and water diffusion through delipidized stratum corneum (middle curve).

From Scheuplein & Blank 144
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Article Title: Permeability of the Skin
 

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Robert J. Scheuplein. Permeability of the Skin. Compr Physiol 2011, Supplement 26: Handbook of Physiology, Reactions to Environmental Agents: 299-322. First published in print 1977. doi: 10.1002/cphy.cp090119