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Chemical penetration enhancers in stratum corneum - Relation between molecular effects and barrier function

Pham, Dat LU ; Björklund, Sebastian LU ; Engblom, Johan; Topgaard, Daniel LU and Sparr, Emma LU (2016) In Journal of Controlled Release 232. p.175-187
Abstract

Skin is attractive for drug therapy because it offers an easily accessible route without first-pass metabolism. Transdermal drug delivery is also associated with high patient compliance and through the site of application, the drug delivery can be locally directed. However, to succeed with transdermal drug delivery it is often required to overcome the low permeability of the upper layer of the skin, the stratum corneum (SC). One common strategy is to employ so-called penetration enhancers that supposedly act to increase the drug passage across SC. Still, there is a lack of understanding of the molecular effects of so-called penetration enhancers on the skin barrier membrane, the SC. In this study, we provide a molecular characterization... (More)

Skin is attractive for drug therapy because it offers an easily accessible route without first-pass metabolism. Transdermal drug delivery is also associated with high patient compliance and through the site of application, the drug delivery can be locally directed. However, to succeed with transdermal drug delivery it is often required to overcome the low permeability of the upper layer of the skin, the stratum corneum (SC). One common strategy is to employ so-called penetration enhancers that supposedly act to increase the drug passage across SC. Still, there is a lack of understanding of the molecular effects of so-called penetration enhancers on the skin barrier membrane, the SC. In this study, we provide a molecular characterization of how different classes of compounds, suggested as penetration enhancers, influence lipid and protein components in SC. The compounds investigated include monoterpenes, fatty acids, osmolytes, surfactant, and Azone. We employ natural abundance 13C polarization transfer solid-state nuclear magnetic resonance (NMR) on intact porcine SC. With this method it is possible to detect small changes in the mobility of the minor fluid lipid and protein SC components, and simultaneously obtain information on the major fraction of solid SC components. The balance between fluid and solid components in the SC is essential to determine macroscopic material properties of the SC, including barrier and mechanical properties. We study SC at different hydration levels corresponding to SC in ambient air and under occlusion. The NMR studies are complemented with diffusion cell experiments that provide quantitative data on skin permeability when treated with different compounds. By correlating the effects on SC molecular components and SC barrier function, we aim at deepened understanding of diffusional transport in SC, and how this can be controlled, which can be utilized for optimal design of transdermal drug delivery formulations.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Diffusion cell, Fatty acid, Keratin filament, Monoterpene, Solid-state NMR, Stratum corneum lipids
in
Journal of Controlled Release
volume
232
pages
13 pages
publisher
Elsevier
external identifiers
  • Scopus:84967214111
  • WOS:000377401000018
ISSN
0168-3659
DOI
10.1016/j.jconrel.2016.04.030
language
English
LU publication?
yes
id
396286fa-58dd-48fd-a776-ec8afd60d165
date added to LUP
2016-06-30 13:02:33
date last changed
2017-02-05 04:51:21
@article{396286fa-58dd-48fd-a776-ec8afd60d165,
  abstract     = {<p>Skin is attractive for drug therapy because it offers an easily accessible route without first-pass metabolism. Transdermal drug delivery is also associated with high patient compliance and through the site of application, the drug delivery can be locally directed. However, to succeed with transdermal drug delivery it is often required to overcome the low permeability of the upper layer of the skin, the stratum corneum (SC). One common strategy is to employ so-called penetration enhancers that supposedly act to increase the drug passage across SC. Still, there is a lack of understanding of the molecular effects of so-called penetration enhancers on the skin barrier membrane, the SC. In this study, we provide a molecular characterization of how different classes of compounds, suggested as penetration enhancers, influence lipid and protein components in SC. The compounds investigated include monoterpenes, fatty acids, osmolytes, surfactant, and Azone. We employ natural abundance <sup>13</sup>C polarization transfer solid-state nuclear magnetic resonance (NMR) on intact porcine SC. With this method it is possible to detect small changes in the mobility of the minor fluid lipid and protein SC components, and simultaneously obtain information on the major fraction of solid SC components. The balance between fluid and solid components in the SC is essential to determine macroscopic material properties of the SC, including barrier and mechanical properties. We study SC at different hydration levels corresponding to SC in ambient air and under occlusion. The NMR studies are complemented with diffusion cell experiments that provide quantitative data on skin permeability when treated with different compounds. By correlating the effects on SC molecular components and SC barrier function, we aim at deepened understanding of diffusional transport in SC, and how this can be controlled, which can be utilized for optimal design of transdermal drug delivery formulations.</p>},
  author       = {Pham, Dat and Björklund, Sebastian and Engblom, Johan and Topgaard, Daniel and Sparr, Emma},
  issn         = {0168-3659},
  keyword      = {Diffusion cell,Fatty acid,Keratin filament,Monoterpene,Solid-state NMR,Stratum corneum lipids},
  language     = {eng},
  month        = {06},
  pages        = {175--187},
  publisher    = {Elsevier},
  series       = {Journal of Controlled Release},
  title        = {Chemical penetration enhancers in stratum corneum - Relation between molecular effects and barrier function},
  url          = {http://dx.doi.org/10.1016/j.jconrel.2016.04.030},
  volume       = {232},
  year         = {2016},
}