TY - JOUR A1 - Wollenberger, Ursula A1 - Neumann, B. A1 - Scheller, Frieder W. T1 - Enzyme and microbial sensors for environmental Monitoring Y1 - 1993 ER - 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 - GEN 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 - Calderón, Marcelo A1 - Hedtrich, Sarah A1 - Schäfer-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 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 335 KW - Drug delivery KW - nanoparticles KW - particle characterization KW - keratinocytes KW - nanotoxicology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-395325 ER - TY - JOUR A1 - Grott, Matthias A1 - Knollenberg, J. A1 - Hamm, M. A1 - Ogawa, K. A1 - Jaumann, R. A1 - Otto, Katharina Alexandra A1 - Delbo, M. A1 - Michel, Patrick A1 - Biele, J. A1 - Neumann, Wladimir A1 - Knapmeyer, Martin A1 - Kührt, E. A1 - Senshu, H. A1 - Okada, T. A1 - Helbert, Jorn A1 - Maturilli, A. A1 - Müller, N. A1 - Hagermann, A. A1 - Sakatani, Naoya A1 - Tanaka, S. A1 - Arai, T. A1 - Mottola, Stefano A1 - Tachibana, Shogo A1 - Pelivan, Ivanka A1 - Drube, Line A1 - Vincent, J-B A1 - Yano, Hajime A1 - Pilorget, C. A1 - Matz, K. D. A1 - Schmitz, N. A1 - Koncz, A. A1 - Schröder, Stefan E. A1 - Trauthan, F. A1 - Schlotterer, Markus A1 - Krause, C. A1 - Ho, T-M A1 - Moussi-Soffys, A. T1 - Low thermal conductivity boulder with high porosity identified on C-type asteroid (162173) Ryugu JF - Nature astronomy N2 - C-type asteroids are among the most pristine objects in the Solar System, but little is known about their interior structure and surface properties. Telescopic thermal infrared observations have so far been interpreted in terms of a regolith-covered surface with low thermal conductivity and particle sizes in the centimetre range. This includes observations of C-type asteroid (162173) Ryugu1,2,3. However, on arrival of the Hayabusa2 spacecraft at Ryugu, a regolith cover of sand- to pebble-sized particles was found to be absent4,5 (R.J. et al., manuscript in preparation). Rather, the surface is largely covered by cobbles and boulders, seemingly incompatible with the remote-sensing infrared observations. Here we report on in situ thermal infrared observations of a boulder on the C-type asteroid Ryugu. We found that the boulder’s thermal inertia was much lower than anticipated based on laboratory measurements of meteorites, and that a surface covered by such low-conductivity boulders would be consistent with remote-sensing observations. Our results furthermore indicate high boulder porosities as well as a low tensile strength in the few hundred kilopascal range. The predicted low tensile strength confirms the suspected observational bias6 in our meteorite collections, as such asteroidal material would be too frail to survive atmospheric entry7 Y1 - 2019 U6 - https://doi.org/10.1038/s41550-019-0832-x SN - 2397-3366 VL - 3 IS - 11 SP - 971 EP - 976 PB - Nature Publishing Group CY - London ER - TY - JOUR A1 - Grott, Matthias A1 - Knollenberg, J. A1 - Hamm, M. A1 - Ogawa, K. A1 - Jaumann, R. A1 - Otto, Katharina Alexandra A1 - Delbo, M. A1 - Michel, P. A1 - Biele, J. A1 - Neumann, W. A1 - Knapmeyer, M. A1 - Kuehrt, E. A1 - Senshu, H. A1 - Okada, T. A1 - Helbert, J. A1 - Maturilli, A. A1 - Müller, N. A1 - Hagermann, A. A1 - Sakatani, N. A1 - Tanaka, S. A1 - Arai, T. A1 - Mottola, S. A1 - Tachibana, S. A1 - Pelivan, Ivanka A1 - Drube, L. A1 - Vincent, J-B A1 - Yano, H. A1 - Pilorget, C. A1 - Matz, K. D. A1 - Schmitz, N. A1 - Koncz, A. A1 - Schröder, S. E. A1 - Trauthan, F. A1 - Schlotterer, M. A1 - Krause, C. A1 - Ho, T-M A1 - Moussi-Soffys, A. T1 - Low thermal conductivity boulder with high porosity identified on C-type asteroid (162173) Ryugu JF - Nature astronomy N2 - C-type asteroids are among the most pristine objects in the Solar System, but little is known about their interior structure and surface properties. Telescopic thermal infrared observations have so far been interpreted in terms of a regolith-covered surface with low thermal conductivity and particle sizes in the centimetre range. This includes observations of C-type asteroid (162173) Ryugu1,2,3. However, on arrival of the Hayabusa2 spacecraft at Ryugu, a regolith cover of sand- to pebble-sized particles was found to be absent4,5 (R.J. et al., manuscript in preparation). Rather, the surface is largely covered by cobbles and boulders, seemingly incompatible with the remote-sensing infrared observations. Here we report on in situ thermal infrared observations of a boulder on the C-type asteroid Ryugu. We found that the boulder’s thermal inertia was much lower than anticipated based on laboratory measurements of meteorites, and that a surface covered by such low-conductivity boulders would be consistent with remote-sensing observations. Our results furthermore indicate high boulder porosities as well as a low tensile strength in the few hundred kilopascal range. The predicted low tensile strength confirms the suspected observational bias6 in our meteorite collections, as such asteroidal material would be too frail to survive atmospheric entry7. Y1 - 2020 U6 - https://doi.org/10.1038/s41550-019-0832-x SN - 2397-3366 VL - 3 IS - 11 SP - 971 EP - 976 PB - Nature Publishing Group CY - London ER -