Nanocrystals for Improved Drug Delivery of Dexamethasone in Skin Investigated by EPR Spectroscopy
Silke B. Lohan,
Siavash Saeidpour,
Miriam Colombo,
Sven Staufenbiel,
Michael Unbehauen,
Amanuel Wolde-Kidan,
Roland R. Netz,
Roland Bodmeier,
Rainer Haag,
Christian Teutloff,
Robert Bittl,
Martina C. Meinke
Affiliations
Silke B. Lohan
Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Siavash Saeidpour
Fachbereich Physik, Freie Universität Berlin, 14195 Berlin, Germany
Miriam Colombo
Pharmazeutische Technologie, Institut für Pharmazie, Freie Universität Berlin, 14195 Berlin, Germany
Sven Staufenbiel
Pharmazeutische Technologie, Institut für Pharmazie, Freie Universität Berlin, 14195 Berlin, Germany
Michael Unbehauen
Institut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, Germany
Amanuel Wolde-Kidan
Fachbereich Physik, Freie Universität Berlin, 14195 Berlin, Germany
Roland R. Netz
Fachbereich Physik, Freie Universität Berlin, 14195 Berlin, Germany
Roland Bodmeier
Pharmazeutische Technologie, Institut für Pharmazie, Freie Universität Berlin, 14195 Berlin, Germany
Rainer Haag
Institut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, Germany
Christian Teutloff
Fachbereich Physik, Freie Universität Berlin, 14195 Berlin, Germany
Robert Bittl
Fachbereich Physik, Freie Universität Berlin, 14195 Berlin, Germany
Martina C. Meinke
Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Nanocrystals represent an improvement over the traditional nanocarriers for dermal application, providing the advantages of 100% drug loading, a large surface area, increased adhesion, and the potential for hair follicle targeting. To investigate their advantage for drug delivery, compared to a base cream formulation, dexamethasone (Dx), a synthetic glucocorticoid frequently used for the treatment of inflammatory skin diseases, was covalently linked with the paramagnetic probe 3-(carboxy)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA) to DxPCA. To investigate the penetration efficiency between these two vehicles, electron paramagnetic resonance (EPR) spectroscopy was used, which allows the quantification of a spin-labeled drug in different skin layers and the monitoring of the drug release. The penetration behavior in excised healthy and barrier-disrupted porcine skin was monitored by EPR, and subsequently analyzed using a numerical diffusion model. As a result, diffusion constants and free energy values in the different layers of the skin were identified for both formulations. Dx-nanocrystals showed a significantly increased drug amount that penetrated into viable epidermis and dermis of intact (factor 3) and barrier-disrupted skin (factor 2.1) compared to the base cream formulation. Furthermore, the observed fast delivery of the spin-labeled drug into the skin (80% DxPCA within 30 min) and a successive release from the aggregate unit into the viable tissue makes these nanocrystals very attractive for clinical applications.
