Penetration Depth of Propylene Glycol, Sodium Fluorescein and Nile Red into the Skin Using Non-Invasive Two-Photon Excited FLIM
Mohammad Alhibah,
Marius Kröger,
Sabine Schanzer,
Loris Busch,
Jürgen Lademann,
Ingeborg Beckers,
Martina C. Meinke,
Maxim E. Darvin
Affiliations
Mohammad Alhibah
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venerology and Allergology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Marius Kröger
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venerology and Allergology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Sabine Schanzer
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venerology and Allergology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Loris Busch
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venerology and Allergology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Jürgen Lademann
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venerology and Allergology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Ingeborg Beckers
Department of Mathematics, Physics and Chemistry, Berliner Hochschule für Technik, Luxemburger Straße 10, 13353 Berlin, Germany
Martina C. Meinke
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venerology and Allergology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Maxim E. Darvin
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venerology and Allergology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
The stratum corneum (SC) forms a strong barrier against topical drug delivery. Therefore, understanding the penetration depth and pathways into the SC is important for the efficiency of drug delivery and cosmetic safety. In this study, TPT-FLIM (two-photon tomography combined with fluorescence lifetime imaging) was applied as a non-invasive optical method for the visualization of skin structure and components to study penetration depths of exemplary substances, like hydrophilic propylene glycol (PG), sodium fluorescein (NaFl) and lipophilic Nile red (NR) into porcine ear skin ex vivo. Non-fluorescent PG was detected indirectly based on the pH-dependent increase in the fluorescence lifetime of SC components. The pH similarity between PG and viable epidermis limited the detection of PG. NaFl reached the viable epidermis, which was also proved by laser scanning microscopy. Tape stripping and confocal Raman micro-spectroscopy were performed additionally to study NaFl, which revealed penetration depths of ≈5 and ≈8 μm, respectively. Lastly, NR did not permeate the SC. We concluded that the amplitude-weighted mean fluorescence lifetime is the most appropriate FLIM parameter to build up penetration profiles. This work is anticipated to provide a non-invasive TPT-FLIM method for studying the penetration of topically applied drugs and cosmetics into the skin.
