@article{RadbruchPischonOstrowskietal.2017,
  author    = {Radbruch, Moritz and Pischon, Hannah and Ostrowski, Anja and Volz, Pierre and Brodwolf, Robert and Neumann, Falko and Unbehauen, Michael and Kleuser, Burkhard and Haag, Rainer and Ma, Nan and Alexiev, Ulrike and Mundhenk, Lars and Gruber, Achim D.},
  title     = {Dendritic core-multishell nanocarriers in murine models of healthy and atopic skin},
  series = {Nanoscale Research Letters},
  volume    = {12},
  journal   = {Nanoscale Research Letters},
  number    = {64},
  publisher = {Springer},
  address   = {New York},
  issn      = {1556-276X},
  doi       = {10.1186/s11671-017-1835-0},
  pages     = {12},
  year      = {2017},
  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.},
  language  = {en}
}
@article{EdlichVolzBrodwolfetal.2018,
  author    = {Edlich, Alexander and Volz, Pierre and Brodwolf, Robert and Unbehauen, Michael and Mundhenk, Lars and Gruber, Achim D. and Hedtrich, Sarah and Haag, Rainer and Alexiev, Ulrike and Kleuser, Burkhard},
  title     = {Crosstalk between core-multishell nanocarriers for cutaneous drug delivery and antigen-presenting cells of the skin},
  series = {Biomaterials : biomaterials reviews online},
  volume    = {162},
  journal   = {Biomaterials : biomaterials reviews online},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0142-9612},
  doi       = {10.1016/j.biomaterials.2018.01.058},
  pages     = {60 -- 70},
  year      = {2018},
  abstract  = {Owing their unique chemical and physical properties core-multishell (CMS) nanocarriers are thought to underlie their exploitable biomedical use for a topical treatment of skin diseases. This highlights the need to consider not only the efficacy of CMS nanocarriers but also the potentially unpredictable and adverse consequences of their exposure thereto. As CMS nanocarriers are able to penetrate into viable layers of normal and stripped human skin ex vivo as well as in in vitro skin disease models the understanding of nanoparticle crosstalk with components of the immune system requires thorough investigation. Our studies highlight the biocompatible properties of CMS nanocarriers on Langerhans cells of the skin as they did neither induce cytotoxicity and genotoxicity nor cause reactive oxygen species (ROS) or an immunological response. Nevertheless, CMS nanocarriers were efficiently taken up by Langerhans cells via divergent endocytic pathways. Bioimaging of CMS nanocarriers by fluorescence lifetime imaging microscopy (FLIM) and flow cytometry indicated not only a localization within the lysosomes but also an energy-dependent exocytosis of unmodified CMS nanocarriers into the extracellular environment. (C) 2018 Elsevier Ltd. All rights reserved.},
  language  = {en}
}
@misc{RadbruchPischonOstrowskietal.2017,
  author    = {Radbruch, Moritz and Pischon, Hannah and Ostrowski, Anja and Volz, Pierre and Brodwolf, Robert and Neumann, Falko and Unbehauen, Michael and Kleuser, Burkhard and Haag, Rainer and Ma, Nan and Alexiev, Ulrike and Mundhenk, Lars and Gruber, Achim D.},
  title     = {Dendritic core-multishell nanocarriers in murine models of healthy and atopic skin},
  series = {Postprints der Universit{\"a}t Potsdam Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam Mathematisch-Naturwissenschaftliche Reihe},
  number    = {724},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43013},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-430136},
  pages     = {12},
  year      = {2017},
  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.},
  language  = {en}
}
@article{WanjikuYamamotoKlosseketal.2019,
  author    = {Wanjiku, Barbara and Yamamoto, Kenji and Klossek, Andre and Schumacher, Fabian and Pischon, Hannah and Mundhenk, Lars and Rancan, Fiorenza and Judd, Martyna M. and Ahmed, Muniruddin and Zoschke, Christian and Kleuser, Burkhard and R{\"u}hl, Eckart and Sch{\"a}fer-Korting, Monika},
  title     = {Qualifying X-ray and Stimulated Raman Spectromicroscopy for Mapping Cutaneous Drug Penetration},
  series = {Analytical chemistry},
  volume    = {91},
  journal   = {Analytical chemistry},
  number    = {11},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {0003-2700},
  doi       = {10.1021/acs.analchem.9b00519},
  pages     = {7208 -- 7214},
  year      = {2019},
  abstract  = {Research on topical drug delivery relies on reconstructed human skin (RHS) in addition to ex vivo human and animal skin, each with specific physiological features. Here, we compared the penetration of dexamethasone from an ethanolic hydroxyethyl cellulose gel into ex vivo human skin, murine skin, and RHS. For comprehensive insights into skin morphology and penetration enhancing mechanisms, scanning transmission X-ray microscopy (STXM), liquid chromatography tandem mass spectrometry (LC-MS/MS), and stimulated Raman spectromicroscopy (SRS) were combined. STXM offers high spatial resolution with label-free drug detection and is therefore sensitive to tissue damage. Despite differences in sample preparation and data analysis, the amounts of dexamethasone in RHS, detected and quantified by STXM and LC-MS/MS, were very similar and increased during the first 100 min of exposure. SRS revealed interactions between the gel and the stratum corneum or, more specifically, its protein and lipid structures. Similar to both types of ex vivo skin, higher protein-to-lipid ratios within the stratum corneum of RHS indicated reduced lipid amounts after 30 min of ethanol exposure. Extended ethanol exposure led to a continued reduction of lipids in the ex vivo matrixes, while protein integrity appeared to be compromised in RHS, which led to declining protein signals. In conclusion, LC-MS/MS proved the predictive capability of STXM for label-free drug detection. Combining STXM with SRS precisely dissected the penetration enhancing effects of ethanol. Further studies on topical drug delivery should consider the potential of these complementary techniques.},
  language  = {en}
}
@misc{PischonRadbruchOstrowskietal.2017,
  author    = {Pischon, Hannah and Radbruch, Moritz and Ostrowski, Anja and Schumacher, Fabian and Hoenzke, Stefan and Kleuser, Burkhard and Hedtrich, Sarah and Fluhr, Joachim W. and Gruber, Achim D. and Mundhenk, Lars},
  title     = {How Effective Is Tacrolimus in the Imiquimod},
  series = {The journal of investigative dermatology},
  volume    = {138},
  journal   = {The journal of investigative dermatology},
  number    = {2},
  publisher = {Elsevier},
  address   = {New York},
  issn      = {0022-202X},
  doi       = {10.1016/j.jid.2017.09.019},
  pages     = {455 -- 458},
  year      = {2017},
  language  = {en}
}