title: Localization of dexamethasone within dendritic core-multishell (CMS) nanoparticles and skin penetration properties studied by multi-frequency electron paramagnetic resonance (EPR) spectroscopy.
abstract: The skin and especially the stratum corneum (SC) act as a barrier and protect epidermal cells and thus the whole body against xenobiotica of the external environment. Topical skin treatment requires an efficient drug delivery system (DDS). Polymer-based nanocarriers represent novel transport vehicles for dermal application of drugs. In this study dendritic core-multishell (CMS) nanoparticles were investigated as promising candidates. CMS nanoparticles were loaded with a drug (analogue) and were applied to penetration studies of skin. We determined by dual-frequency electron paramagnetic resonance (EPR) how dexamethasone (Dx) labelled with 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA) is associated with the CMS. The micro-environment of the drug loaded to CMS nanoparticles was investigated by pulsed high-field EPR at cryogenic temperature, making use of the fact that magnetic parameters (g-, A-matrices, and spin-lattice relaxation time) represent specific probes for the micro-environment. Additionally, the rotational correlation time of spin-labelled Dx was probed by continuous wave EPR at ambient temperature, which provides independent information on the drug environment. Furthermore, the penetration depth of Dx into the stratum corneum of porcine skin after different topical applications was investigated. The location of Dx in the CMS nanoparticles is revealed and the function of CMS as penetration enhancers for topical application is shown.
authors.affiliation: Berlin Joint EPR Laboratory, Freie Universität Berlin, Fachbereich Physik, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Saeidpour
authors.affiliation: Charité - Universitätsmedizin Berlin, Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Berlin, Germany.
authors.forename: S B
authors.initials: SB
authors.lastname: Lohan
authors.affiliation: Berlin Joint EPR Laboratory, Freie Universität Berlin, Fachbereich Physik, Berlin, Germany; Charité - Universitätsmedizin Berlin, Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Anske
authors.affiliation: Freie Universität Berlin, Institut für Chemie und Biochemie, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Unbehauen
authors.affiliation: Freie Universität Berlin, Institut für Chemie und Biochemie, Berlin, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Fleige
authors.affiliation: Freie Universität Berlin, Institut für Chemie und Biochemie, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Haag
authors.affiliation: Charité - Universitätsmedizin Berlin, Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology, Berlin, Germany.
authors.forename: M C
authors.initials: MC
authors.lastname: Meinke
authors.affiliation: Berlin Joint EPR Laboratory, Freie Universität Berlin, Fachbereich Physik, Berlin, Germany. Electronic address: robert.bittl@fu-berlin.de.
authors.forename: R
authors.initials: R
authors.lastname: Bittl
authors.affiliation: Berlin Joint EPR Laboratory, Freie Universität Berlin, Fachbereich Physik, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Teutloff
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D003907:Dexamethasone / Q000737:chemistry* / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D013113:Spin Labels; D013552:Swine
chemical_list: D004337:Drug Carriers; D011108:Polymers; D013113:Spin Labels; D003907:Dexamethasone
keywords: Dendritic core-multishell (CMS) systems; Dexamethasone; Drug delivery system (DDS); Dual-frequency EPR; Mobility; Skin penetration; Solvent polarity