dc.contributor.author
Schulz, Robert
dc.contributor.author
Yamamoto, Kenji
dc.contributor.author
Klossek, André
dc.contributor.author
Flesch, Roman
dc.contributor.author
Hönzke, Stefan
dc.contributor.author
Rancan, Fiorenza
dc.contributor.author
Vogt, Annika
dc.contributor.author
Blume-Peytavi, Ulrike
dc.contributor.author
Hedtrich, Sarah
dc.contributor.author
Schäfer-Korting, Monika
dc.contributor.author
Rühl, Eckart
dc.contributor.author
Netz, Roland R.
dc.date.accessioned
2018-12-13T11:34:14Z
dc.date.available
2018-12-13T11:34:14Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/23569
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-1355
dc.description.abstract
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.
en
dc.format.extent
6 S. (Artikel); 4 S. (Supprting Information)
dc.rights.uri
http://www.fu-berlin.de/sites/refubium/rechtliches/Nutzungsbedingungen
dc.subject
diffusion, data-based modeling, biological barriers, skin, Smoluchowski equation
en
dc.subject
data-based modeling
en
dc.subject
biological barriers
en
dc.subject
Smoluchowski equation
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::530 Physik::530 Physik
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik
dc.title
Data-based modeling of drug penetration relates human skin barrier function to the interplay of diffusivity and free-energy profiles
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1073/pnas.1620636114
dcterms.bibliographicCitation.journaltitle
Proceedings of the National Academy of Sciences
dcterms.bibliographicCitation.number
14
dcterms.bibliographicCitation.pagestart
3631
dcterms.bibliographicCitation.pageend
3636
dcterms.bibliographicCitation.volume
114
dcterms.bibliographicCitation.url
https://doi.org/10.1073/pnas.1620636114
dcterms.rightsHolder.note
PNAS open access option
dcterms.rightsHolder.url
https://www.pnas.org/page/subscriptions/open-access
refubium.affiliation
Physik
refubium.affiliation.other
Institut für Theoretische Physik
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refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.issn
0027-8424 (Print)
dcterms.isPartOf.issn
1091-6490 (Online)