title: Core-multishell nanocarriers: Transport and release of dexamethasone probed by soft X-ray spectromicroscopy.
abstract: Label-free detection of core-multishell (CMS) nanocarriers and the anti-inflammatory drug dexamethasone is reported. Selective excitation by tunable soft X-rays in the O 1s-regime is used for probing either the CMS nanocarrier or the drug. Furthermore, the drug loading efficiency into CMS nanocarriers is determined by X-ray spectroscopy. The drug-loaded nanocarriers were topically applied to human skin explants providing insights into the penetration and drug release processes. It is shown that the core-multishell nanocarriers remain in the stratum corneum when applied for 100min to 1000min. Dexamethasone, if applied topically to human ex vivo skin explants using different formulations, shows a vehicle-dependent penetration behavior. Highest local drug concentrations are found in the stratum corneum as well as in the viable epidermis. If the drug is loaded to core-multishell nanocarriers, the concentration of the free drug is low in the stratum corneum and is enhanced in the viable epidermis as compared to other drug formulations. The present results provide insights into the penetration of drug nanocarriers as well as the mechanisms of controlled drug release from CMS nanocarriers in human skin. They are also compared to related work using dye-labeled nanocarriers and dyes that were used as model drugs.
authors: Physikalische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
authors: K
authors: K
authors: Yamamoto
authors: Physikalische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
authors: A
authors: A
authors: Klossek
authors: Physikalische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
authors: R
authors: R
authors: Flesch
authors: UVSOR Synchrotron Facility, Institute for Molecular Science, Okazaki 444-8585, Japan.
authors: T
authors: T
authors: Ohigashi
authors: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
authors: E
authors: E
authors: Fleige
authors: Klinisches Forschungszentrum für Haut- und Haarforschung, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: F
authors: F
authors: Rancan
authors: Klinisches Forschungszentrum für Haut- und Haarforschung, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: J
authors: J
authors: Frombach
authors: Klinisches Forschungszentrum für Haut- und Haarforschung, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: A
authors: A
authors: Vogt
authors: Klinisches Forschungszentrum für Haut- und Haarforschung, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: U
authors: U
authors: Blume-Peytavi
authors: Abteilung für Elektronenmikroskopie at CVK, 13353 Berlin, Germany.
authors: P
authors: P
authors: Schrade
authors: Abteilung für Elektronenmikroskopie at CVK, 13353 Berlin, Germany.
authors: S
authors: S
authors: Bachmann
authors: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
authors: R
authors: R
authors: Haag
authors: Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Str. 2-4, 14195 Berlin, Germany.
authors: S
authors: S
authors: Hedtrich
authors: Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Str. 2-4, 14195 Berlin, Germany.
authors: M
authors: M
authors: Schäfer-Korting
authors: UVSOR Synchrotron Facility, Institute for Molecular Science, Okazaki 444-8585, Japan.
authors: N
authors: N
authors: Kosugi
authors: Physikalische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany. Electronic address: ruehl@zedat.fu-berlin.de.
authors: E
authors: E
authors: Rühl
mesh_terms: D000279:Administration, Cutaneous; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001692:Biological Transport; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D018625:Microscopy, Atomic Force / Q000379:methods; D053758:Nanoparticles; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013997:Time Factors; D056928:X-Ray Absorption Spectroscopy / Q000379:methods
chemical_list: D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D003907:Dexamethasone
keywords: Core-multishell nanocarriers; Drug delivery; Human skin; X-ray microscopy