title: Influence of the skin barrier on the penetration of topically-applied dexamethasone probed by soft X-ray spectromicroscopy.
abstract: The penetration of dexamethasone into human skin ex vivo is reported. X-ray microscopy is used for label-free probing of the drug and quantification of the local drug concentration with a spatial resolution reaching 70±5nm. This is accomplished by selective probing the dexamethasone by X-ray absorption. Varying the penetration time between 10min and 1000min provides detailed information on the penetration process. In addition, the stratum corneum has been damaged by tape-stripping in order to determine the importance of this barrier regarding temporally resolved drug penetration profiles. Dexamethasone concentrations distinctly vary, especially close to the border of the stratum corneum and the viable epidermis, where a local minimum in drug concentration is observed. Furthermore, near the basal membrane the drug concentration strongly drops. High spatial resolution studies along with a de-convolution procedure reveal the spatial distribution of dexamethasone in the interspaces between the corneocytes consisting of stratum corneum lipids. These results on local drug concentrations are interpreted in terms of barriers affecting the drug penetration in human skin.
authors.affiliation: Physikalische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Physikalische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Klossek
authors.affiliation: Physikalische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Flesch
authors.affiliation: Klinisches Forschungszentrum für Haut- und Haarforschung, Charité Universitätsmedizin, Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Rancan
authors.affiliation: Max-Planck-Institut für Metallforschung, Heisenbergstraβe 3, 70569 Stuttgart, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Weigand
authors.affiliation: Max-Planck-Institut für Metallforschung, Heisenbergstraβe 3, 70569 Stuttgart, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Bykova
authors.affiliation: Max-Planck-Institut für Metallforschung, Heisenbergstraβe 3, 70569 Stuttgart, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bechtel
authors.affiliation: Klinisches Forschungszentrum für Haut- und Haarforschung, Charité Universitätsmedizin, Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ahlberg
authors.affiliation: Klinisches Forschungszentrum für Haut- und Haarforschung, Charité Universitätsmedizin, Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Vogt
authors.affiliation: Klinisches Forschungszentrum für Haut- und Haarforschung, Charité Universitätsmedizin, Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Blume-Peytavi
authors.affiliation: Abteilung für Elektronenmikroskopie at Campus Virchow Klinikum (CVK), Charité Universitätsmedizin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Schrade
authors.affiliation: Abteilung für Elektronenmikroskopie at Campus Virchow Klinikum (CVK), Charité Universitätsmedizin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Bachmann
authors.affiliation: Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hedtrich
authors.affiliation: Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schäfer-Korting
authors.affiliation: Physikalische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany. Electronic address: ruehl@zedat.fu-berlin.de.
authors.forename: E
authors.initials: E
authors.lastname: Rühl
mesh_terms: D000279:Administration, Cutaneous; D003907:Dexamethasone / Q000494:pharmacology*; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008853:Microscopy / Q000379:methods*; D012869:Skin Absorption; D013057:Spectrum Analysis / Q000379:methods*; D014965:X-Rays
chemical_list: D008055:Lipids; D003907:Dexamethasone
keywords: Drug delivery; Drug penetration; Skin; Skin barrier; X-ray microscopy