title: Stratum corneum targeting by dendritic core-multishell-nanocarriers in a mouse model of psoriasis.
abstract: Inflammatory disorders of the skin pose particular therapeutic challenges due to complex structural and functional alterations of the skin barrier. Penetration of several anti-inflammatory drugs is particularly problematic in psoriasis, a common dermatitis condition with epidermal hyperplasia and hyperkeratosis. Here, we tested in vivo dermal penetration and biological effects of dendritic core-multishell-nanocarriers (CMS) in a murine skin model of psoriasis and compared it to healthy skin. In both groups, CMS exclusively localized to the stratum corneum of the epidermis with only very sporadic uptake by Langerhans cells. Furthermore, penetration into the viable epidermis of nile red as a model for lipophilic compounds was enhanced by CMS. CMS proved fully biocompatible in several in vitro assays and on normal and psoriatic mouse skin. The observations support the concept of CMS as promising candidates for drug delivery in inflammatory hyperkeratotic skin disorders in vivo.
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Pischon
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Radbruch
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Ostrowski
authors.affiliation: Department of Physics, Institute of Experimental Physics, Freie Universität Berlin, Berlin, Germany.
authors.forename: Pierre
authors.initials: P
authors.lastname: Volz
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gerecke
authors.affiliation: Institute of Chemistry and Biochemistry, Organic Chemistry, Freie Universität Berlin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Unbehauen
authors.affiliation: Institute for Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hönzke
authors.affiliation: Institute for Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Berlin, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hedtrich
authors.affiliation: Department of Dermatology, Venerology and Allergology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Fluhr
authors.affiliation: Institute of Chemistry and Biochemistry, Organic Chemistry, Freie Universität Berlin, Berlin, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kleuser
authors.affiliation: Department of Physics, Institute of Experimental Physics, Freie Universität Berlin, Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Alexiev
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany. Electronic address: lars.mundhenk@fu-berlin.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Mundhenk
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry*; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D011565:Psoriasis / Q000188:drug therapy*; D012869:Skin Absorption
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers
keywords: CMS; FLIM; Fluorescence microscopy; Mouse model; Nile red