title: Penetration of normal, damaged and diseased skin--an in vitro study on dendritic core-multishell nanotransporters.
abstract: A growing intended or accidental exposure to nanoparticles asks for the elucidation of potential toxicity linked to the penetration of normal and lesional skin. We studied the skin penetration of dye-tagged dendritic core-multishell (CMS) nanotransporters and of Nile red loaded CMS nanotransporters using fluorescence microscopy. Normal and stripped human skin ex vivo as well as normal reconstructed human skin and in vitro skin disease models served as test platforms. Nile red was delivered rapidly into the viable epidermis and dermis of normal skin, whereas the highly flexible CMS nanotransporters remained solely in the stratum corneum after 6h but penetrated into deeper skin layers after 24h exposure. Fluorescence lifetime imaging microscopy proved a stable dye-tag and revealed striking nanotransporter-skin interactions. The viable layers of stripped skin were penetrated more efficiently by dye-tagged CMS nanotransporters and the cargo compared to normal skin. Normal reconstructed human skin reflected the penetration of Nile red and CMS nanotransporters in human skin and both, the non-hyperkeratotic non-melanoma skin cancer and hyperkeratotic peeling skin disease models come along with altered absorption in the skin diseases.
authors.affiliation: Institute for Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Berlin, Germany.
authors.forename: Nesrin
authors.initials: N
authors.lastname: Alnasif
authors.affiliation: Institute for Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Zoschke
authors.affiliation: Institute of Chemistry and Biochemistry (Organic Chemistry), Freie Universität Berlin, Berlin, Germany.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Fleige
authors.affiliation: Institute of Experimental Physics, Freie Universität Berlin, Berlin, Germany; Helmholtz Virtual Institute - Multifuntional Biomaterials for Medicine, Helmholtz Zentrum Geesthacht, Teltow, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Brodwolf
authors.affiliation: Institute of Experimental Physics, Freie Universität Berlin, Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Boreham
authors.affiliation: Institute of Chemistry and Biochemistry (Physical and Theoretical Chemistry), Freie Universität Berlin, Berlin, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Rühl
authors.affiliation: University of Cologne, Cologne Center for Genomics, Cologne, Germany; Dermatogenetics, Div. of Human Genetics, Dept. of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Katja-Martina
authors.initials: KM
authors.lastname: Eckl
authors.affiliation: Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Hans-Friedrich
authors.initials: HF
authors.lastname: Merk
authors.affiliation: University of Cologne, Cologne Center for Genomics, Cologne, Germany; Dermatogenetics, Div. of Human Genetics, Dept. of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Hennies
authors.affiliation: Institute of Experimental Physics, Freie Universität Berlin, Berlin, Germany; Helmholtz Virtual Institute - Multifuntional Biomaterials for Medicine, Helmholtz Zentrum Geesthacht, Teltow, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Alexiev
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 for Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Berlin, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Küchler
authors.affiliation: Institute for Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Berlin, Germany. Electronic address: monika.schaefer-korting@fu-berlin.de.
authors.forename: Monika
authors.initials: M
authors.lastname: Schäfer-Korting
mesh_terms: D004337:Drug Carriers / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000032:analysis / Q000378:metabolism*; D010078:Oxazines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012869:Skin Absorption; D012871:Skin Diseases / Q000378:metabolism / Q000473:pathology
chemical_list: D004337:Drug Carriers; D010078:Oxazines; C044808:nile red
keywords: Dendritic core–multishell nanotransporters; Nanotoxicology; Non-melanoma skin cancer; Peeling skin syndrome; Reconstructed human skin; Skin absorption