TY  - JOUR
A1  - Brachner, Andreas
A1  - Fragouli, Despina
A1  - Duarte, Iola F.
A1  - Farias, Patricia M. A.
A1  - Dembski, Sofia
A1  - Ghosh, Manosij
A1  - Barisic, Ivan
A1  - Zdzieblo, Daniela
A1  - Vanoirbeek, Jeroen
A1  - Schwabl, Philipp
A1  - Neuhaus, Winfried
T1  - Assessment of human health risks posed by nano-and microplastics is currently not feasible
JF  - International Journal of Environmental Research and Public Health
N2  - The exposure of humans to nano-and microplastic particles (NMPs) is an issue recognized as a potential health hazard by scientists, authorities, politics, non-governmental organizations and the general public. The concentration of NMPs in the environment is increasing concomitantly with global plastic production and the usage of plastic materials. NMPs are detectable in numerous aquatic organisms and also in human samples, therefore necessitating a risk assessment of NMPs for human health. So far, a comprehensive risk assessment of NMPs is hampered by limited availability of appropriate reference materials, analytical obstacles and a lack of definitions and standardized study designs. Most studies conducted so far used polystyrene (PS) spheres as a matter of availability, although this polymer type accounts for only about 7% of total plastic production. Differently sized particles, different concentration and incubation times, and various biological models have been used, yielding hardly comparable data sets. Crucial physico-chemical properties of NMPs such as surface (charge, polarity, chemical reactivity), supplemented additives and adsorbed chemicals have been widely excluded from studies, although in particular the surface of NMPs determines the interaction with cellular membranes. In this manuscript we give an overview about the critical parameters which should be considered when performing risk assessments of NMPs, including novel reference materials, taking into account surface modifications (e.g., reflecting weathering processes), and the possible role of NMPs as a substrate and/or carrier for (pathogenic) microbes. Moreover, we make suggestions for biological model systems to evaluate immediate toxicity, long-term effects and the potential of NMPs to cross biological barriers. We are convinced that standardized reference materials and experimental parameters along with technical innovations in (nano)-particle sampling and analytics are a prerequisite for the successful realization of conclusive human health risk assessments of NMPs.
KW  - nanoplastics
KW  - nanoparticles
KW  - microplastics
KW  - microparticles
KW  - human exposure
KW  - biological barriers
KW  - biofilm
KW  - microbe carrier
KW  - toxicity
KW  - neurotoxicity
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219423
SN  - 1660-4601
VL  - 17
IS  - 23
ER  - 
TY  - JOUR
A1  - Appelt‐Menzel, Antje
A1  - Oerter, Sabrina
A1  - Mathew, Sanjana
A1  - Haferkamp, Undine
A1  - Hartmann, Carla
A1  - Jung, Matthias
A1  - Neuhaus, Winfried
A1  - Pless, Ole
T1  - Human iPSC‐Derived Blood‐Brain Barrier Models: Valuable Tools for Preclinical Drug Discovery and Development?
JF  - Current Protocols in Stem Cell Biology
N2  - Translating basic biological knowledge into applications remains a key issue for effectively tackling neurodegenerative, neuroinflammatory, or neuroendocrine disorders. Efficient delivery of therapeutics across the neuroprotective blood‐brain barrier (BBB) still poses a demanding challenge for drug development targeting central nervous system diseases. Validated in vitro models of the BBB could facilitate effective testing of drug candidates targeting the brain early in the drug discovery process during lead generation. We here review the potential of mono‐ or (isogenic) co‐culture BBB models based on brain capillary endothelial cells (BCECs) derived from human‐induced pluripotent stem cells (hiPSCs), and compare them to several available BBB in vitro models from primary human or non‐human cells and to rodent in vivo models, as well as to classical and widely used barrier models [Caco‐2, parallel artificial membrane permeability assay (PAMPA)]. In particular, we are discussing the features and predictivity of these models and how hiPSC‐derived BBB models could impact future discovery and development of novel CNS‐targeting therapeutics.
KW  - blood‐brain barrier (BBB)
KW  - CNS disease
KW  - drug permeability screening
KW  - human‐induced pluripotent stem cells (hiPSC)
KW  - preclinical drug discovery
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218509
VL  - 55
IS  - 1
ER  -