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Dendritic core-multishell nanocarriers in murine models of healthy and atopic skin

  • 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 wereDendritic 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.show moreshow less

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Author:Moritz Radbruch, Hannah PischonGND, Anja OstrowskiGND, Pierre Volz, Robert Brodwolf, Falko Neumann, Michael UnbehauenGND, Burkhard KleuserORCiDGND, Rainer HaagORCiDGND, Nan Ma, Ulrike Alexiev, Lars MundhenkORCiDGND, Achim D. Gruber
URN:urn:nbn:de:kobv:517-opus4-430136
DOI:https://doi.org/10.25932/publishup-43013
ISSN:1866-8372
Parent Title (German):Postprints der Universität Potsdam Mathematisch-Naturwissenschaftliche Reihe
Series (Serial Number):Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (724)
Document Type:Postprint
Language:English
Date of first Publication:2019/06/14
Year of Completion:2017
Publishing Institution:Universität Potsdam
Release Date:2019/06/14
Tag:CMS; atopic dermatitis; dermal delivery; fluorescence lifetime imaging microscopy; multi-domain nanoparticles; nanomaterials; oxazolone; penetration enhancement; skin; topical treatment
Issue:724
Pagenumber:12
Source:Nanoscale Research Letters 12 (2017) 64 DOI: 10.1186/s11671-017-1835-0
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 60 Technik / 600 Technik, Technologie
Peer Review:Referiert
Publication Way:Open Access
Licence (German):License LogoCreative Commons - Namensnennung, 4.0 International