title: Dendritic Core-Multishell Nanocarriers in Murine Models of Healthy and Atopic Skin.
abstract: Dendritic hPG-amid-C18-mPEG core-multishell nanocarriers (CMS) represent a novel class of unimolecular micelles that hold great potential as drug transporters, e.g., to facilitate topical therapy in skin diseases. Atopic dermatitis is among the most common inflammatory skin disorders with complex barrier alterations which may affect the efficacy of topical treatment.Here, we tested the penetration behavior and identified target structures of unloaded CMS after topical administration in healthy mice and in mice with oxazolone-induced atopic dermatitis. We further examined whole body distribution and possible systemic side effects after simulating high dosage dermal penetration by subcutaneous injection.Following topical administration, CMS accumulated in the stratum corneum without penetration into deeper viable epidermal layers. The same was observed in atopic dermatitis mice, indicating that barrier alterations in atopic dermatitis had no influence on the penetration of CMS. Following subcutaneous injection, CMS were deposited in the regional lymph nodes as well as in liver, spleen, lung, and kidney. However, in vitro toxicity tests, clinical data, and morphometry-assisted histopathological analyses yielded no evidence of any toxic or otherwise adverse local or systemic effects of CMS, nor did they affect the severity or course of atopic dermatitis.Taken together, CMS accumulate in the stratum corneum in both healthy and inflammatory skin and appear to be highly biocompatible in the mouse even under conditions of atopic dermatitis and thus could potentially serve to create a depot for anti-inflammatory drugs in the skin.
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, 14163, Berlin, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Radbruch
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, 14163, Berlin, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Pischon
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, 14163, Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Ostrowski
authors.affiliation: Institute of Experimental Physics, Department of Physics, Freie Universität Berlin, Berlin, Germany.
authors.forename: Pierre
authors.initials: P
authors.lastname: Volz
authors.affiliation: Institute of Experimental Physics, Department of Physics, Freie Universität Berlin, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Brodwolf
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany.
authors.forename: Falko
authors.initials: F
authors.lastname: Neumann
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 of Nutritional Science, University of Potsdam, Nuthetal, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kleuser
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 Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany.
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.affiliation: Institute of Experimental Physics, Department of Physics, Freie Universität Berlin, Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Alexiev
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, 14163, Berlin, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Mundhenk
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, 14163, Berlin, Germany. achim.gruber@fu-berlin.de.
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
keywords: Atopic dermatitis; CMS; Dermal delivery; Fluorescence lifetime imaging microscopy; Multi-domain nanoparticles; Nanomaterials; Oxazolone; Penetration enhancement; Skin; Topical treatment