@article{ZhangSaidWischkeetal.2017, author = {Zhang, Nan and Said, Andre and Wischke, Christian and Kral, Vivian and Brodwolf, Robert and Volz, Pierre and Boreham, Alexander and Gerecke, Christian and Li, Wenzhong and Neffe, Axel T. and Kleuser, Burkhard and Alexiev, Ulrike and Lendlein, Andreas and Sch{\"a}fer-Korting, Monika}, title = {Poly[acrylonitrile-co-(N-vinyl pyrrolidone)] nanoparticles - Composition-dependent skin penetration enhancement of a dye probe and biocompatibility}, series = {European Journal of Pharmaceutics and Biopharmaceutics}, volume = {116}, journal = {European Journal of Pharmaceutics and Biopharmaceutics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0939-6411}, doi = {10.1016/j.ejpb.2016.10.019}, pages = {66 -- 75}, year = {2017}, abstract = {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.}, language = {en} } @article{GereckeEdlichGiulbudagianetal.2017, author = {Gerecke, Christian and Edlich, Alexander and Giulbudagian, Michael and Schumacher, Fabian and Zhang, Nan and Said, Andre and Yealland, Guy and Lohan, Silke B. and Neumann, Falko and Meinke, Martina C. and Ma, Nan and Calderon, Marcelo and Hedtrich, Sarah and Schaefer-Korting, Monika and Kleuser, Burkhard}, title = {Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes}, series = {Nanotoxicology}, volume = {11}, journal = {Nanotoxicology}, publisher = {Routledge, Taylor \& Francis Group}, address = {Abingdon}, issn = {1743-5390}, doi = {10.1080/17435390.2017.1292371}, pages = {267 -- 277}, year = {2017}, abstract = {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.}, language = {en} } @misc{GereckeEdlichGiulbudagianetal.2017, author = {Gerecke, Christian and Edlich, Alexander and Giulbudagian, Michael and Schumacher, Fabian and Zhang, Nan and Said, Andre and Yealland, Guy and Lohan, Silke B. and Neumann, Falko and Meinke, Martina C. and Ma, Nan and Calder{\´o}n, Marcelo and Hedtrich, Sarah and Sch{\"a}fer-Korting, Monika and Kleuser, Burkhard}, title = {Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-395325}, pages = {11}, year = {2017}, abstract = {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.}, language = {en} } @article{TuckerBoehningGaeseFaganetal.2018, author = {Tucker, Marlee A. and Boehning-Gaese, Katrin and Fagan, William F. and Fryxell, John M. and Van Moorter, Bram and Alberts, Susan C. and Ali, Abdullahi H. and Allen, Andrew M. and Attias, Nina and Avgar, Tal and Bartlam-Brooks, Hattie and Bayarbaatar, Buuveibaatar and Belant, Jerrold L. and Bertassoni, Alessandra and Beyer, Dean and Bidner, Laura and van Beest, Floris M. and Blake, Stephen and Blaum, Niels and Bracis, Chloe and Brown, Danielle and de Bruyn, P. J. Nico and Cagnacci, Francesca and Calabrese, Justin M. and Camilo-Alves, Constanca and Chamaille-Jammes, Simon and Chiaradia, Andre and Davidson, Sarah C. and Dennis, Todd and DeStefano, Stephen and Diefenbach, Duane and Douglas-Hamilton, Iain and Fennessy, Julian and Fichtel, Claudia and Fiedler, Wolfgang and Fischer, Christina and Fischhoff, Ilya and Fleming, Christen H. and Ford, Adam T. and Fritz, Susanne A. and Gehr, Benedikt and Goheen, Jacob R. and Gurarie, Eliezer and Hebblewhite, Mark and Heurich, Marco and Hewison, A. J. Mark and Hof, Christian and Hurme, Edward and Isbell, Lynne A. and Janssen, Rene and Jeltsch, Florian and Kaczensky, Petra and Kane, Adam and Kappeler, Peter M. and Kauffman, Matthew and Kays, Roland and Kimuyu, Duncan and Koch, Flavia and Kranstauber, Bart and LaPoint, Scott and Leimgruber, Peter and Linnell, John D. C. and Lopez-Lopez, Pascual and Markham, A. Catherine and Mattisson, Jenny and Medici, Emilia Patricia and Mellone, Ugo and Merrill, Evelyn and Mourao, Guilherme de Miranda and Morato, Ronaldo G. and Morellet, Nicolas and Morrison, Thomas A. and Diaz-Munoz, Samuel L. and Mysterud, Atle and Nandintsetseg, Dejid and Nathan, Ran and Niamir, Aidin and Odden, John and Oliveira-Santos, Luiz Gustavo R. and Olson, Kirk A. and Patterson, Bruce D. and de Paula, Rogerio Cunha and Pedrotti, Luca and Reineking, Bjorn and Rimmler, Martin and Rogers, Tracey L. and Rolandsen, Christer Moe and Rosenberry, Christopher S. and Rubenstein, Daniel I. and Safi, Kamran and Said, Sonia and Sapir, Nir and Sawyer, Hall and Schmidt, Niels Martin and Selva, Nuria and Sergiel, Agnieszka and Shiilegdamba, Enkhtuvshin and Silva, Joao Paulo and Singh, Navinder and Solberg, Erling J. and Spiegel, Orr and Strand, Olav and Sundaresan, Siva and Ullmann, Wiebke and Voigt, Ulrich and Wall, Jake and Wattles, David and Wikelski, Martin and Wilmers, Christopher C. and Wilson, John W. and Wittemyer, George and Zieba, Filip and Zwijacz-Kozica, Tomasz and Mueller, Thomas}, title = {Moving in the Anthropocene}, series = {Science}, volume = {359}, journal = {Science}, number = {6374}, publisher = {American Assoc. for the Advancement of Science}, address = {Washington}, issn = {0036-8075}, doi = {10.1126/science.aam9712}, pages = {466 -- 469}, year = {2018}, abstract = {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.}, language = {en} }