Skin Permeability

Schaefer, H.; Zesch, A; Stüttgen, Günter

doi:10.1007/978-3-642-68734-1

Cited by 112 publications

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“…1A): the epidermis with a thickness of about 100 µm, which prevents water loss and the entrance of harmful microorganisms or irritants, and the dermis, which is typically 2 mm thick, contains blood vessels, and protects the body from mechanical stress (4). The epidermis is further divided into the stratum corneum (SC), the 10-to 20-µm thick outermost layer consisting of dried-out dead skin cells, the corneocytes, and the viable epidermis (VE).…”

mentioning

confidence: 99%

Data-based modeling of drug penetration relates human skin barrier function to the interplay of diffusivity and free-energy profiles

Schulz

Yamamoto

Klossek

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Based on experimental concentration depth profiles of the antiinflammatory drug dexamethasone in human skin, we model the time-dependent drug penetration by the 1D general diffusion equation that accounts for spatial variations in the diffusivity and free energy. For this, we numerically invert the diffusion equation and thereby obtain the diffusivity and the free-energy profiles of the drug as a function of skin depth without further model assumptions. As the only input, drug concentration profiles derived from X-ray microscopy at three consecutive times are used. For dexamethasone, skin barrier function is shown to rely on the combination of a substantially reduced drug diffusivity in the stratum corneum (the outermost epidermal layer), dominant at short times, and a pronounced free-energy barrier at the transition from the epidermis to the dermis underneath, which determines the drug distribution in the long-time limit. Our modeling approach, which is generally applicable to all kinds of barriers and diffusors, allows us to disentangle diffusivity from free-energetic effects. Thereby we can predict short-time drug penetration, where experimental measurements are not feasible, as well as long-time permeation, where ex vivo samples deteriorate, and thus span the entire timescales of biological barrier functioning.M ulticellular organisms exhibit numerous structurally distinct protective barriers, such as the blood-brain barrier; intestinal, mouth, and respiratory mucosa; and the skin, the largest human organ. These barriers are generally designed to keep foreign material out and in some cases to allow the highly regulated transfer of certain desired molecules; consequently, they present a severe challenge for drug delivery (1-3). The indepth understanding of barrier function is not only required for controlled drug delivery, but also of central interest in medicine, drug development, and biology.Human skin can be broadly divided into two layers (Fig. 1A): the epidermis with a thickness of about 100 µm, which prevents water loss and the entrance of harmful microorganisms or irritants, and the dermis, which is typically 2 mm thick, contains blood vessels, and protects the body from mechanical stress (4). The epidermis is further divided into the stratum corneum (SC), the 10-to 20-µm thick outermost layer consisting of dried-out dead skin cells, the corneocytes, and the viable epidermis (VE). In the stratum granulosum (SG), which is part of the VE, skin cells (keratinocytes) are gradually flattened and transformed into corneocytes when migrating toward the SC.The SC is structurally similar to a brick wall (5): The bricks are the corneocytes, whereas the mortar is the intercellular matrix, which is composed of stacked lipid bilayers. Several models for the permeation of drugs through skin exist, which incorporate the skin structure on different levels of complexity. In the simplest models the stratified skin structure is reflected by 1D layers with different diffusivities and partition coefficients (6-10), and in ...

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mentioning

confidence: 99%

Data-based modeling of drug penetration relates human skin barrier function to the interplay of diffusivity and free-energy profiles

Schulz

Yamamoto

Klossek

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Especially for polar substances, the resistance to permeation is considerably lower than in the stratum corneum and the active substance permeates easily to the dermis, which consists of connective tissue and contains blood vessels, lymph vessels and nerves [1] . Chemicals reaching the dermis are readily absorbed into the bloodstream and may act systemically [1,6] . Finally, the dermis is located on the subcutis, which is made of a network of fat cells [6] .…”

Section: Review Articlementioning

confidence: 99%

“…Chemicals reaching the dermis are readily absorbed into the bloodstream and may act systemically [1,6] . Finally, the dermis is located on the subcutis, which is made of a network of fat cells [6] .…”

Section: Review Articlementioning

confidence: 99%

“…The percutaneous absorption process may be divided into three steps: penetration, which is entry of the active substance into a particular layer or organ and diffusion within that layer or organ; permeation, which is the penetration through one layer to another, which is both functionally and structurally different from the first layer; absorption, which is the uptake of the active substance into the vascular system [1,6] .…”

Section: Review Articlementioning

confidence: 99%

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Dermal and Transdermal Delivery of Active Substances from Semisolid Bases

Jankowski¹,

Dyja²,

Sarecka-Hujar³

2017

pharmaceutical-sciences

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Jankowski, et al.: Dermal and Transdermal Delivery from SemisolidsThe selection of a semisolid base type (hydrophobic, hydrophilic or emulsion) has an essential influence on the skin and transdermal delivery of active substances. The cutaneous and percutaneous absorption may be influenced by interactions occurring between base components and skin on the one hand and interactions between base components and the active ingredient on the other hand. The present article discusses the utility of different types of semisolid bases as carriers of active substances and summarizes results of studies comparing delivery of active substances from different semisolid bases.

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“…Skin permeability investigations are com monly performed via study of the inward penetration of chemicals through the skin [1,2], Recently, this laboratory has introduced a method for the study of skin permeability from the inside out, based on the use of a noninvasive transdermal chemical collection device (TCD) [3]. The features and perfor mance of this device have been documented in studies of both volatile and nonvolatile compounds, and have been utilized in studies with humans [4], rodents [5], and monkeys [3].…”

Section: Introductionmentioning

confidence: 99%

Noninvasive Transdermal Chemical Collection. II. In vitro and in vivo Skin Permeability Studies

Bradley

Almirez²,

Conner³

et al. 1990

Skin Pharmacol Physiol

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In vitro and in vivo skin permeability studies were conducted to investigate properties of several candidate transdermal chemical collection devices (TCDs). The TCD consists of a binding reservoir of activated charcoal suspended in a gel medium which is occlusively placed in direct contact with the skin. Binding of three model compounds (theophylline, methotrexate, and parathion) was studied in hydrophilic (agarose or PVA/PVP) and lipophilic (silicone) gel/carbon compositions. The effects of gel composition, compound hydrophilicity/lipophilicity, and hydration of skin on quantity of transdermally collected chemical and ‘apparent’ permeability were investigated using a ‘fuzzy’ rat animal model. In vitro and in vivo apparent permeability coefficients (K_p; cm/h) for amphophilic theophylline (6.95 0^-4 and 8.34 10^-4, respectively) and hydrophilic methotrexate (3.5 10^-3 and 3.2 10^-4, respectively) using an agarose aquagel TCD were greater than the corresponding K_p values obtained when silicone lipogel TCDs were employed (0.3 10^-4 and 3.2 10^-4, respectively, for theophylline; no measurable methotrexate was collected). Occlusive hydration of skin profoundly increased permeability of the hydrophyilic model compound, methotrexate. In vivo K_p values for lipophilic parathion were greater with a silicone TCD (6.7 10^-4) than with an agarose TCD (3.8 10^-4). We conclude that it is possible to influence transdermal chemical collection through modifications in the gel composition and by hydration of the skin.

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Skin Permeability

Cited by 112 publications

References 0 publications

Data-based modeling of drug penetration relates human skin barrier function to the interplay of diffusivity and free-energy profiles

Data-based modeling of drug penetration relates human skin barrier function to the interplay of diffusivity and free-energy profiles

Dermal and Transdermal Delivery of Active Substances from Semisolid Bases

Noninvasive Transdermal Chemical Collection. II. In vitro and in vivo Skin Permeability Studies

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