Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels
Fiorenza Rancan,
Hildburg Volkmann,
Michael Giulbudagian,
Fabian Schumacher,
Jessica Isolde Stanko,
Burkhard Kleuser,
Ulrike Blume-Peytavi,
Marcelo Calderón,
Annika Vogt
Affiliations
Fiorenza Rancan
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Hildburg Volkmann
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Michael Giulbudagian
Institut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, Germany
Fabian Schumacher
Institute of Nutritional Science, Department of Nutritional Toxicology, University of Potsdam, 14558 Nuthetal, Germany
Jessica Isolde Stanko
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Burkhard Kleuser
Institute of Nutritional Science, Department of Nutritional Toxicology, University of Potsdam, 14558 Nuthetal, Germany
Ulrike Blume-Peytavi
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Marcelo Calderón
Institut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, Germany
Annika Vogt
Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions.
