In vivo methods for the analysis of the penetration of topically applied substances in and through the skin barrier

Authors

  • J. Lademann,

    Corresponding author
    • Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology (CCP), Charité – Universitätsmedizin Berlin, Berlin, Germany
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  • M. C. Meinke,

    1. Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology (CCP), Charité – Universitätsmedizin Berlin, Berlin, Germany
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  • S. Schanzer,

    1. Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology (CCP), Charité – Universitätsmedizin Berlin, Berlin, Germany
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  • H. Richter,

    1. Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology (CCP), Charité – Universitätsmedizin Berlin, Berlin, Germany
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  • M. E. Darvin,

    1. Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology (CCP), Charité – Universitätsmedizin Berlin, Berlin, Germany
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  • S. F. Haag,

    1. Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology (CCP), Charité – Universitätsmedizin Berlin, Berlin, Germany
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  • J. W. Fluhr,

    1. Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology (CCP), Charité – Universitätsmedizin Berlin, Berlin, Germany
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  • H.-J. Weigmann,

    1. Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology (CCP), Charité – Universitätsmedizin Berlin, Berlin, Germany
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  • W. Sterry,

    1. Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology (CCP), Charité – Universitätsmedizin Berlin, Berlin, Germany
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  • A. Patzelt

    1. Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology (CCP), Charité – Universitätsmedizin Berlin, Berlin, Germany
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Correspondence: Jürgen Lademann, Department of Dermatology, Venerology and Allergology, Center of Experimental an Applied Cutaneous Physiology (CCP), Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Tel.: ++49 (0) 30 4505 18100; fax: ++49 (0) 30 4505 18918; e-mail: juergen.lademann@charite.de

Synopsis

The efficacy of a drug is characterized by its action mechanism and its ability to pass the skin barrier. In this article, different methods are discussed, which permit this penetration process to be analysed non-invasively. Providing qualitative and quantitative information, tape stripping is one of the oldest procedures for penetration studies. Although single cell layers of corneocytes are removed from the skin surface, this procedure is considered as non-invasive and is applicable exclusively to the stratum corneum. Recently, optical and spectroscopic methods have been used to investigate the penetration process. Fluorescence-labelled drugs can be easily detected in the skin by laser scanning microscopy. This method has the disadvantage that the dye labelling changes the molecular structures of the drug and consequently might influence the penetration properties. The penetration process of non-fluorescent substances can be analysed by Raman spectroscopy, electron paramagnetic resonance, CARS and multiphoton microscopic measurements. Using these methods, the concentration of the topically applied formulations in different depths of the stratum corneum can be detected by moving the laser focus from the skin surface deeper into the stratum corneum. The advantages and disadvantages of these methods will be discussed in this article.

Résumé

L'efficacité d'un médicament se caractérise par son mécanisme d'action et sa capacité à passer la barrière de la peau. Dans le présent document les différentes méthodes sont discutées, qui permettent d'analyser le processus de la pénétration de façon non invasive. L'arrachage (tape stripping) est l'une des plus anciennes méthodes pour les études de pénétration puisqu'elle fournit de l'information qualitative et quantitative. Bien que des cellules isolées des couches de cornéocytes soient retirées de la surface de la peau, cette procédure est considérée comme non-invasive; elle est applicable exclusivement à la couche cornée. Récemment, des méthodes spectroscopiques et optiques et ont été utilisées pour étudier le processus de pénétration. Les médicaments marqués par fluorescence peuvent être détectés facilement dans la peau par la microscopie à balayage laser. Cette méthode présente l'inconvénient que le label coloré change les structures moléculaires de la drogue et par conséquent sont susceptibles d'influencer les propriétés de pénétration. Le processus de pénétration des substances non-fluorescentes peut être analysé par spectroscopie Raman, par la résonance paramagnétique électronique, CARS et par des mesures de microscopie multiphotonique. En utilisant ces méthodes, la concentration des formulations topiques à des profondeurs différentes du stratum corneum peut être détectée par le déplacement du focus laser à partir de la surface de la peau vers les couches plus profondes de la couche cornée. Les avantages et les inconvénients de ces méthodes seront discutés dans le présent document.

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