Microdialysis on Ex Vivo Porcine Ear Skin Can Validly Study Dermal Penetration including the Fraction of Transfollicular Penetration—Demonstrated on Caffeine Nanocrystals
Anna Lena Klein,
Markus Lubda,
David Specht,
Sung-Min Pyo,
Loris Busch,
Jürgen Lademann,
Martina C. Meinke,
Ingeborg Beckers,
Jörg von Hagen,
Cornelia M. Keck,
Alexa Patzelt
Affiliations
Anna Lena Klein
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology Venereology and Allergology, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité—Universitätsmedizin, 10117 Berlin, Germany
Markus Lubda
Merck KGaA, 64293 Darmstadt, Germany
David Specht
Department of Pharmaceutics and Biopharmaceutics, Philipps-Universität, 35037 Marburg, Germany
Sung-Min Pyo
BASF SE, R&D Pharma Ingredients, 67063 Ludwigshafen, Germany
Loris Busch
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology Venereology and Allergology, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité—Universitätsmedizin, 10117 Berlin, Germany
Jürgen Lademann
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology Venereology and Allergology, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité—Universitätsmedizin, 10117 Berlin, Germany
Martina C. Meinke
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology Venereology and Allergology, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité—Universitätsmedizin, 10117 Berlin, Germany
Ingeborg Beckers
Department II, Beuth University of Applied Sciences, 13353 Berlin, Germany
Jörg von Hagen
Merck KGaA, 64293 Darmstadt, Germany
Cornelia M. Keck
Department of Pharmaceutics and Biopharmaceutics, Philipps-Universität, 35037 Marburg, Germany
Alexa Patzelt
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology Venereology and Allergology, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité—Universitätsmedizin, 10117 Berlin, Germany
Common ex vivo methods for penetration investigations often fail to monitor transfollicular penetration appropriately. In the present investigation, the validity of dermal microdialysis on the ex vivo porcine ear skin to investigate penetration kinetics, including transfollicular penetration, was studied. In setup A, a caffeine nanocrystal formulation was compared to a non-particular caffeine gel formulation. In setup B, two caffeine nanocrystal formulations of different sizes (200 nm, 700 nm) were compared to each other. Microdialysis samples were collected for 46 h. After sampling, the skin layers were separated, homogenized, and caffeine was quantified in all samples. In setup A the area under the curve (AUC) after crystal gel formulation application was 12 times higher than after non-particular formulation application. Setup B showed an increased AUC of 42% in the microdialysis data when the 700 nm caffeine crystals were applied compared to the 200 nm crystals. The microdialysis data was supported by the separation, homogenization and extraction data. Microdialysis performed on ex vivo porcine ear skin is a novel experimental setup. It is of high interest for further investigations since it is able to also capture the impact of follicular and transfollicular penetration kinetics as no other ex vivo setup can.
