TY - JOUR A1 - Zhang, Nan A1 - Said, Andre A1 - Wischke, Christian A1 - Kral, Vivian A1 - Brodwolf, Robert A1 - Volz, Pierre A1 - Boreham, Alexander A1 - Gerecke, Christian A1 - Li, Wenzhong A1 - Neffe, Axel T. A1 - Kleuser, Burkhard A1 - Alexiev, Ulrike A1 - Lendlein, Andreas A1 - Schäfer-Korting, Monika T1 - Poly[acrylonitrile-co-(N-vinyl pyrrolidone)] nanoparticles - Composition-dependent skin penetration enhancement of a dye probe and biocompatibility JF - European Journal of Pharmaceutics and Biopharmaceutics N2 - Nanoparticles can improve topical drug delivery: size, surface properties and flexibility of polymer nanoparticles are defining its interaction with the skin. Only few studies have explored skin penetration for one series of structurally related polymer particles with systematic alteration of material composition. Here, a series of rigid poly[acrylonitrile-co-(N-vinyl pyrrolidone)] model nanoparticles stably loaded with Nile Red or Rhodamin B, respectively, was comprehensively studied for biocompatibility and functionality. Surface properties were altered by varying the molar content of hydrophilic NVP from 0 to 24.1% and particle size ranged from 35 to 244 nm. Whereas irritancy and genotoxicity were not revealed, lipophilic and hydrophilic nanoparticles taken up by keratinocytes affected cell viability. Skin absorption of the particles into viable skin ex vivo was studied using Nile Red as fluorescent probe. Whilst an intact stratum corneum efficiently prevented penetration, almost complete removal of the horny layer allowed nanoparticles of smaller size and hydrophilic particles to penetrate into viable epidermis and dermis. Hence, systematic variations of nanoparticle properties allows gaining insights into critical criteria for biocompatibility and functionality of novel nanocarriers for topical drug delivery and risks associated with environmental exposure. KW - Biocompatibility testing KW - Drug delivery systems KW - Nanoparticle KW - Poly[acrylonitrile-co-(N-vinyl pyrrolidone)] KW - Polymers KW - Skin absorption Y1 - 2017 U6 - https://doi.org/10.1016/j.ejpb.2016.10.019 SN - 0939-6411 SN - 1873-3441 VL - 116 SP - 66 EP - 75 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Tucker, Marlee A. A1 - Boehning-Gaese, Katrin A1 - Fagan, William F. A1 - Fryxell, John M. A1 - Van Moorter, Bram A1 - Alberts, Susan C. A1 - Ali, Abdullahi H. A1 - Allen, Andrew M. A1 - Attias, Nina A1 - Avgar, Tal A1 - Bartlam-Brooks, Hattie A1 - Bayarbaatar, Buuveibaatar A1 - Belant, Jerrold L. A1 - Bertassoni, Alessandra A1 - Beyer, Dean A1 - Bidner, Laura A1 - van Beest, Floris M. A1 - Blake, Stephen A1 - Blaum, Niels A1 - Bracis, Chloe A1 - Brown, Danielle A1 - de Bruyn, P. J. Nico A1 - Cagnacci, Francesca A1 - Calabrese, Justin M. A1 - Camilo-Alves, Constanca A1 - Chamaille-Jammes, Simon A1 - Chiaradia, Andre A1 - Davidson, Sarah C. A1 - Dennis, Todd A1 - DeStefano, Stephen A1 - Diefenbach, Duane A1 - Douglas-Hamilton, Iain A1 - Fennessy, Julian A1 - Fichtel, Claudia A1 - Fiedler, Wolfgang A1 - Fischer, Christina A1 - Fischhoff, Ilya A1 - Fleming, Christen H. A1 - Ford, Adam T. A1 - Fritz, Susanne A. A1 - Gehr, Benedikt A1 - Goheen, Jacob R. A1 - Gurarie, Eliezer A1 - Hebblewhite, Mark A1 - Heurich, Marco A1 - Hewison, A. J. Mark A1 - Hof, Christian A1 - Hurme, Edward A1 - Isbell, Lynne A. A1 - Janssen, Rene A1 - Jeltsch, Florian A1 - Kaczensky, Petra A1 - Kane, Adam A1 - Kappeler, Peter M. A1 - Kauffman, Matthew A1 - Kays, Roland A1 - Kimuyu, Duncan A1 - Koch, Flavia A1 - Kranstauber, Bart A1 - LaPoint, Scott A1 - Leimgruber, Peter A1 - Linnell, John D. C. A1 - Lopez-Lopez, Pascual A1 - Markham, A. Catherine A1 - Mattisson, Jenny A1 - Medici, Emilia Patricia A1 - Mellone, Ugo A1 - Merrill, Evelyn A1 - Mourao, Guilherme de Miranda A1 - Morato, Ronaldo G. A1 - Morellet, Nicolas A1 - Morrison, Thomas A. A1 - Diaz-Munoz, Samuel L. A1 - Mysterud, Atle A1 - Nandintsetseg, Dejid A1 - Nathan, Ran A1 - Niamir, Aidin A1 - Odden, John A1 - Oliveira-Santos, Luiz Gustavo R. A1 - Olson, Kirk A. A1 - Patterson, Bruce D. A1 - de Paula, Rogerio Cunha A1 - Pedrotti, Luca A1 - Reineking, Bjorn A1 - Rimmler, Martin A1 - Rogers, Tracey L. A1 - Rolandsen, Christer Moe A1 - Rosenberry, Christopher S. A1 - Rubenstein, Daniel I. A1 - Safi, Kamran A1 - Said, Sonia A1 - Sapir, Nir A1 - Sawyer, Hall A1 - Schmidt, Niels Martin A1 - Selva, Nuria A1 - Sergiel, Agnieszka A1 - Shiilegdamba, Enkhtuvshin A1 - Silva, Joao Paulo A1 - Singh, Navinder A1 - Solberg, Erling J. A1 - Spiegel, Orr A1 - Strand, Olav A1 - Sundaresan, Siva A1 - Ullmann, Wiebke A1 - Voigt, Ulrich A1 - Wall, Jake A1 - Wattles, David A1 - Wikelski, Martin A1 - Wilmers, Christopher C. A1 - Wilson, John W. A1 - Wittemyer, George A1 - Zieba, Filip A1 - Zwijacz-Kozica, Tomasz A1 - Mueller, Thomas T1 - Moving in the Anthropocene BT - global reductions in terrestrial mammalian movements JF - Science N2 - Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission. Y1 - 2018 U6 - https://doi.org/10.1126/science.aam9712 SN - 0036-8075 SN - 1095-9203 VL - 359 IS - 6374 SP - 466 EP - 469 PB - American Assoc. for the Advancement of Science CY - Washington 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 - 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 -