TY  - JOUR
A1  - Gerecke, Christian
A1  - Edlich, Alexander
A1  - Giulbudagian, Michael
A1  - Schumacher, Fabian
A1  - Zhang, Nan
A1  - Said, Andre
A1  - Yealland, Guy
A1  - Lohan, Silke B.
A1  - Neumann, Falko
A1  - Meinke, Martina C.
A1  - Ma, Nan
A1  - Calderon, Marcelo
A1  - Hedtrich, Sarah
A1  - Schaefer-Korting, Monika
A1  - Kleuser, Burkhard
T1  - Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes
JF  - Nanotoxicology
N2  - Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery.
KW  - Drug delivery
KW  - nanoparticles
KW  - particle characterization
KW  - keratinocytes
KW  - nanotoxicology
Y1  - 2017
U6  - https://doi.org/10.1080/17435390.2017.1292371
SN  - 1743-5390
SN  - 1743-5404
VL  - 11
SP  - 267
EP  - 277
PB  - Routledge, Taylor & Francis Group
CY  - Abingdon
ER  - 
TY  - JOUR
A1  - Edlich, Alexander
A1  - Volz, Pierre
A1  - Brodwolf, Robert
A1  - Unbehauen, Michael
A1  - Mundhenk, Lars
A1  - Gruber, Achim D.
A1  - Hedtrich, Sarah
A1  - Haag, Rainer
A1  - Alexiev, Ulrike
A1  - Kleuser, Burkhard
T1  - Crosstalk between core-multishell nanocarriers for cutaneous drug delivery and antigen-presenting cells of the skin
JF  - Biomaterials : biomaterials reviews online
N2  - 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.
KW  - Core-multishell nanocarriers
KW  - Fluorescence lifetime imaging microscopy
KW  - Langerhans cells
KW  - Nanoparticle uptake
KW  - Nanotoxicology
Y1  - 2018
U6  - https://doi.org/10.1016/j.biomaterials.2018.01.058
SN  - 0142-9612
SN  - 1878-5905
VL  - 162
SP  - 60
EP  - 70
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - THES
A1  - Edlich, Alexander
T1  - Interaktionen zwischen Nanotransportern und antigenpräsentierenden Zellen der Haut
Y1  - 2018
ER  -