Filters

2020 - 20236

More filters

2020 - 20246
Reset filters

Settings

search.filters.applied.f.access: openAccess × Author: Kraegeloh, Annette × End date: 2023 × Start date: 2020 × Has files: Yes × Type: Text × WGL Institute: INM ×

Search Results

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Impact of mucus modulation by N-acetylcysteine on nanoparticle toxicity
    (Amsterdam : Elsevier, 2023) Meziu, Enkeleda; Shehu, Kristela; Koch, Marcus; Schneider, Marc; Kraegeloh, Annette
    Human respiratory mucus is a biological hydrogel that forms a protective barrier for the underlying epithelium. Modulation of the mucus layer has been employed as a strategy to enhance transmucosal drug carrier transport. However, a drawback of this strategy is a potential reduction of the mucus barrier properties, in particular in situations with an increased exposure to particles. In this study, we investigated the impact of mucus modulation on its protective role. In vitro mucus was produced by Calu-3 cells, cultivated at the air-liquid interface for 21 days and used for further testing as formed on top of the cells. Analysis of confocal 3D imaging data revealed that after 21 days Calu-3 cells secrete a mucus layer with a thickness of 24 ± 6 μm. Mucus appeared to restrict penetration of 500 nm carboxyl-modified polystyrene particles to the upper 5–10 μm of the layer. Furthermore, a mucus modulation protocol using aerosolized N-acetylcysteine (NAC) was developed. This treatment enhanced the penetration of particles through the mucus down to deeper layers by means of the mucolytic action of NAC. These findings were supported by cytotoxicity data, indicating that intact mucus protects the underlying epithelium from particle-induced effects on membrane integrity. The impact of NAC treatment on the protective properties of mucus was probed by using 50 and 100 nm amine-modified and 50 nm carboxyl-modified polystyrene nanoparticles, respectively. Cytotoxicity was only induced by the amine-modified particles in combination with NAC treatment, implying a reduced protective function of modulated mucus. Overall, our data emphasize the importance of integrating an assessment of the protective function of mucus into the development of therapy approaches involving mucus modulation.
  • Thumbnail Image
    Item
    Digital research data: from analysis of existing standards to a scientific foundation for a modular metadata schema in nanosafety
    (London : BioMed Central, 2022) Elberskirch, Linda; Binder, Kunigunde; Riefler, Norbert; Sofranko, Adriana; Liebing, Julia; Minella, Christian Bonatto; Mädler, Lutz; Razum, Matthias; van Thriel, Christoph; Unfried, Klaus; Schins, Roel P. F.; Kraegeloh, Annette
    Background: Assessing the safety of engineered nanomaterials (ENMs) is an interdisciplinary and complex process producing huge amounts of information and data. To make such data and metadata reusable for researchers, manufacturers, and regulatory authorities, there is an urgent need to record and provide this information in a structured, harmonized, and digitized way. Results: This study aimed to identify appropriate description standards and quality criteria for the special use in nanosafety. There are many existing standards and guidelines designed for collecting data and metadata, ranging from regulatory guidelines to specific databases. Most of them are incomplete or not specifically designed for ENM research. However, by merging the content of several existing standards and guidelines, a basic catalogue of descriptive information and quality criteria was generated. In an iterative process, our interdisciplinary team identified deficits and added missing information into a comprehensive schema. Subsequently, this overview was externally evaluated by a panel of experts during a workshop. This whole process resulted in a minimum information table (MIT), specifying necessary minimum information to be provided along with experimental results on effects of ENMs in the biological context in a flexible and modular manner. The MIT is divided into six modules: general information, material information, biological model information, exposure information, endpoint read out information and analysis and statistics. These modules are further partitioned into module subdivisions serving to include more detailed information. A comparison with existing ontologies, which also aim to electronically collect data and metadata on nanosafety studies, showed that the newly developed MIT exhibits a higher level of detail compared to those existing schemas, making it more usable to prevent gaps in the communication of information. Conclusion: Implementing the requirements of the MIT into e.g., electronic lab notebooks (ELNs) would make the collection of all necessary data and metadata a daily routine and thereby would improve the reproducibility and reusability of experiments. Furthermore, this approach is particularly beneficial regarding the rapidly expanding developments and applications of novel non-animal alternative testing methods.
  • Thumbnail Image
    Item
    Safe-by-Design part II: A strategy for balancing safety and functionality in the different stages of the innovation process
    (Amsterdam : Elsevier, 2021) Tavernaro, Isabella; Dekkers, Susan; Soeteman-Hernández, Lya G.; Herbeck-Engel, Petra; Noorlander, Cornelle; Kraegeloh, Annette
    Manufactured nanomaterials have the potential to impact an exceedingly wide number of industries and markets ranging from energy storage, electronic and optical devices, light-weight construction to innovative medical approaches for diagnostics and therapy. In order to foster the development of safer nanomaterial-containing products, two main aspects are of major interest: their functional performance as well as their safety towards human health and the environment. In this paper a first proposal for a strategy is presented to link the functionality of nanomaterials with safety aspects. This strategy first combines information on the functionality and safety early during the innovation process and onwards, and then identifies Safe-by-Design (SbD) actions that allow for optimisation of both aspects throughout the innovation process. The strategy encompasses suggestions for the type of information needed to balance functionality and safety to support decision making in the innovation process. The applicability of the strategy is illustrated using a literature-based case study on carbon nanotube-based transparent conductive films. This is a first attempt to identify information that can be used for balancing functionality and safety in a structured way during innovation processes.
  • Thumbnail Image
    Item
    How Structured Metadata Acquisition Contributes to the Reproducibility of Nanosafety Studies: Evaluation by a Round-Robin Test
    (Basel : MDPI, 2022) Elberskirch, Linda; Sofranko, Adriana; Liebing, Julia; Riefler, Norbert; Binder, Kunigunde; Bonatto Minella, Christian; Razum, Matthias; Mädler, Lutz; Unfried, Klaus; Schins, Roel P.F.; Kraegeloh, Annette; van Thriel, Christoph
    It has been widely recognized that nanosafety studies are limited in reproducibility, caused by missing or inadequate information and data gaps. Reliable and comprehensive studies should be performed supported by standards or guidelines, which need to be harmonized and usable for the multidisciplinary field of nanosafety research. The previously described minimal information table (MIT), based on existing standards or guidelines, represents one approach towards harmonization. Here, we demonstrate the applicability and advantages of the MIT by a round-robin test. Its modular structure enables describing individual studies comprehensively by a combination of various relevant aspects. Three laboratories conducted a WST-1 cell viability assay using A549 cells to analyze the effects of the reference nanomaterials NM101 and NM110 according to predefined (S)OPs. The MIT contains relevant and defined descriptive information and quality criteria and thus supported the implementation of the round-robin test from planning, investigation to analysis and data interpretation. As a result, we could identify sources of variability and justify deviating results attributed to differences in specific procedures. Consequently, the use of the MIT contributes to the acquisition of reliable and comprehensive datasets and therefore improves the significance and reusability of nanosafety studies
  • Thumbnail Image
    Item
    High-dose intranasal application of titanium dioxide nanoparticles induces the systemic uptakes and allergic airway inflammation in asthmatic mice
    (London : BioMed Central, 2020) Harfoush, Shaza Abdulnasser; Hannig, Matthias; Le, Duc Dung; Heck, Sebastian; Leitner, Maximilian; Omlor, Albert Joachim; Tavernaro, Isabella; Kraegeloh, Annette; Kautenburger, Ralf; Kickelbick, Guido; Beilhack, Andreas; Bischoff, Markus; Nguyen, Juliane; Sester, Martina; Bals, Robert; Dinh, Quoc Thai
    Background Titanium dioxide nanoparticles (TiO2 NPs) have a wide range of applications in several industrial and biomedical domains. Based on the evidence, the workers exposed to inhaled nanosized TiO2 powder are more susceptible to the risks of developing respiratory diseases. Accordingly, this issue has increasingly attracted the researchers’ interest in understanding the consequences of TiO2 NPs exposure. Regarding this, the present study was conducted to analyze the local effects of TiO2 NPs on allergic airway inflammation and their uptake in a mouse model of ovalbumin (OVA)-induced allergic airway inflammation. Methods For the purpose of the study, female BALB/c mice with or without asthma were intranasally administered with TiO2 NPs. The mice were subjected to histological assessment, lung function testing, scanning electron microscopy (SEM), inductively coupled plasma mass spectrometry (ICP-MS), and NP uptake measurement. In addition, T helper (Th) 1/Th2 cytokines were evaluated in the lung homogenate using the enzyme-linked immunosorbent assay. Results According to the results, the mice receiving OVA alone or OVA plus TiO2 NPs showed eosinophilic infiltrates and mucus overproduction in the lung tissues, compared to the controls. Furthermore, a significant elevation was observed in the circulating Th2 cytokines, including interleukin (IL)-4, IL-5, and IL-13 after NP exposure. The TiO2 NPs were taken up by alveolar macrophages at different time points. As the results of the SEM and ICP-MS indicated, TiO2 NPs were present in most of the organs in both asthmatic and non-asthmatic mice. Conclusion Based on the findings of the current study, intranasally or inhalation exposure to high-dose nanosized TiO2 particles appears to exacerbate the allergic airway inflammation and lead to systemic uptake in extrapulmonary organs. These results indicate the very important need to investigate the upper limit of intranasally or inhalation exposure to nanosized TiO2 particles in occupational and environmental health policy.
  • Thumbnail Image
    Item
    Discussion on Existing Standards and Quality Criteria in Nanosafety Research : Summary of the NanoS-QM Expert Workshop
    (Zenodo, 2021) Binder, Kunigunde; Bonatto Minella, Christian; Elberskirchen, Linda; Kraegeloh, Annette; Liebing, Julia; Petzold, Christiane; Razum, Matthias; Riefler, Norbert; Schins, Roel; Sofranko, Adriana; van Thriel, Christoph; Unfried, Klaus
    The partners of the research project NanoS-QM (Quality- and Description Standards for Nanosafety Research Data) identified and invited relevant experts from research institutions, federal agencies, and industry to evaluate the traceability of the results generated with the existing standards and quality criteria. During the discussion it emerged that numerous studies seem to be of insufficient quality for regulatory purposes or exhibit weaknesses with regard to data completeness. Deficiencies in study design could be avoided by more comprehensive use of appropriate standards, many of which already exist. The use of Electronic Laboratory Notebooks (ELNs) that allow for early collection of metadata and enrichment of datasets could be one solution to enable data re-use and simplify quality control. Generally, earlier provision and curation of data and metadata indicating their quality and completeness (e.g. guidelines, standards, standard operating procedures (SOPs) that were used) would improve their findability, accessibility, interoperability, and reusability (FAIR) in the nanosafety research field.