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    Qualifying X-ray and Stimulated Raman Spectromicroscopy for Mapping Cutaneous Drug Penetration (2019)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Wanjiku, Barbara
    Yamamoto, Kenji
    Klossek, André
    Schumacher, Fabian
    Pischon, Hannah
    Mundhenk, Lars (WE 12)
    Rancan, Fiorenza
    Judd, Martyna M
    Ahmed, Muniruddin
    Zoschke, Christian
    Kleuser, Burkhard
    Rühl, Eckart
    Schäfer-Korting, Monika
    Quelle
    Analytical chemistry
    Bandzählung: 91
    Heftzählung: 11
    Seiten: 7208 – 7214
    ISSN: 1520-6882
    Sprache
    Englisch
    Verweise
    DOI: 10.1021/acs.analchem.9b00519
    Pubmed: 31090401
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    14163 Berlin
    +49 30 838 62450
    pathologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Research on topical drug delivery relies on reconstructed human skin (RHS) in addition to ex vivo human and animal skin, each with specific physiological features. Here, we compared the penetration of dexamethasone from an ethanolic hydroxyethyl cellulose gel into ex vivo human skin, murine skin, and RHS. For comprehensive insights into skin morphology and penetration enhancing mechanisms, scanning transmission X-ray microscopy (STXM), liquid chromatography tandem-mass spectrometry (LC-MS/MS), and stimulated Raman spectromicroscopy (SRS) were combined. STXM offers high spatial resolution with label-free drug detection and is therefore sensitive to tissue damage. Despite differences in sample preparation and data analysis, the amounts of dexamethasone in RHS, detected and quantified by STXM and LC-MS/MS, were very similar and increased during the first 100 min of exposure. SRS revealed interactions between the gel and the stratum corneum or, more specifically, its protein and lipid structures. Similar to both types of ex vivo skin, higher protein-to-lipid ratios within the stratum corneum of RHS indicated reduced lipid amounts after 30 min of ethanol exposure. Extended ethanol exposure led to a continued reduction of lipids in the ex vivo matrixes, while protein integrity appeared to be compromised in RHS, which led to declining protein signals. In conclusion, LC-MS/MS proved the predictive capability of STXM for label-free drug detection. Combining STXM with SRS precisely dissected the penetration enhancing effects of ethanol. Further studies on topical drug delivery should consider the potential of these complementary techniques.