Selective Probing of the Penetration of Dexamethasone into Human Skin by Soft X-ray Spectromicroscopy.
Selective probing of dexamethasone in excised human skin using soft X-ray spectromicroscopy provides quantitative concentration profiles as well as two-dimensional drug distribution maps. Element- and site-selective excitation of dexamethasone at the oxygen K-edge with the lateral step width adjusted to 1 μm provides detailed information on the location of the drug in the different skin layers. The key of this work is to probe dexamethasone selectively at the carbonyl site (C3) by the O 1s → π* transition, providing also a most efficient way to quantify the drug concentration as a function of penetration depth in correlation with structural properties of the skin containing carboxyl and amide oxygen sites occurring at higher transition energy than dexamethasone. Following drug exposure for 4 h, the glucocorticoide is located in about equal amounts in the stratum corneum, the outermost horny layer of skin, and in the viable epidermis, whereas in the dermis no dexamethasone is detected. In the stratum corneum, most of the lipophilic drug is found in regions between corneocytes, where epidermal lipids are dominating.
§Physikalische Chemie, Institut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, Takustrasse 3, Germany.
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K
Yamamoto
§Physikalische Chemie, Institut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, Takustrasse 3, Germany.
R
R
Flesch
∥Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Japan.
T
T
Ohigashi
¶Institut für Pharmazie, Freie Universität Berlin, 14195 Berlin, Germany.
S
S
Hedtrich
§Physikalische Chemie, Institut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, Takustrasse 3, Germany.
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A
Klossek
§Physikalische Chemie, Institut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, Takustrasse 3, Germany.
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P
Patoka
§Physikalische Chemie, Institut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, Takustrasse 3, Germany.
G
G
Ulrich
†Klinisches Forschungszentrum für Haut-und Haarforschung, Charité Universitätsmedizin, 10117 Berlin, Germany.
S
S
Ahlberg
†Klinisches Forschungszentrum für Haut-und Haarforschung, Charité Universitätsmedizin, 10117 Berlin, Germany.
F
F
Rancan
†Klinisches Forschungszentrum für Haut-und Haarforschung, Charité Universitätsmedizin, 10117 Berlin, Germany.
A
A
Vogt
†Klinisches Forschungszentrum für Haut-und Haarforschung, Charité Universitätsmedizin, 10117 Berlin, Germany.
U
U
Blume-Peytavi
‡Abteilung für Elektronenmikroskopie at CVK, 13353 Berlin, Germany.
P
P
Schrade
‡Abteilung für Elektronenmikroskopie at CVK, 13353 Berlin, Germany.
S
S
Bachmann
¶Institut für Pharmazie, Freie Universität Berlin, 14195 Berlin, Germany.
M
M
Schäfer-Korting
∥Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Japan.
N
N
Kosugi
§Physikalische Chemie, Institut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, Takustrasse 3, Germany.
E
E
Rühl
D003907:Dexamethasone / Q000737:chemistry / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008968:Molecular Conformation; D012867:Skin / Q000737:chemistry*; D013057:Spectrum Analysis; D014965:X-Rays
D003907:Dexamethasone