Pulmonary in vitro instruments for the replacement of animal experiments

Primavessy, Daniel; Metz, Julia; Schnur, Sabrina; Schneider, Marc; Lehr, Claus‐Michael; Hittinger, Marius

doi:10.1016/j.ejpb.2021.08.005

Cited by 7 publications

(5 citation statements)

References 112 publications

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“…The base module holds another insert for a 6-well QCM. The total surface area of the base being exposed to the aerosol was 190 cm 2 .…”

Section: Setup Of the 96-well Exposure System For Nebulization Of Tes...mentioning

confidence: 99%

“…[1] It is apparent, not only in the field of therapy development, but also in the field of risk assessment of air pollutants -such as particulate matter, dusts, nanoparticles, and chemicals-that there is a great need for test systems that reflect the "real" situation of pollutant exposure or inhalation, both from the biological and the technical application side. [2] In addition, due to ethical aspects and political demands, animal models in pharmaceutical and toxicological testing are being increasingly replaced by animal-free methods, such as advanced in vitro models. Within the scope of the 3R principle of Russell and Burch (replace, reduce, refine), [3] compliance is becoming mandatory in In this study, a 96-well exposure system for safety assessment of nanomaterials is developed and characterized using an air-liquid interface lung epithelial model.…”

Section: Introductionmentioning

confidence: 99%

“…[7,18] Due to its complexity, mechanical devices have been combined with biological models, thereby enabling the exposure of gas or aerosols to cells cultured at an air-liquid-interface (ALI). [2] Until today, most devices that allow "physiological" aerosol exposure of cells have been based on the sedimentation principle, which facilitates cell exposure with the test substance only as non-sequential aerosol exposure and only for up to 48 positions at the same time. [2,[19][20][21][22][23][24][25] When using the flow principle, the maximum number of positions exposed in parallel is limited to 48 samples.…”

Section: Introductionmentioning

confidence: 99%

“…[2] Until today, most devices that allow "physiological" aerosol exposure of cells have been based on the sedimentation principle, which facilitates cell exposure with the test substance only as non-sequential aerosol exposure and only for up to 48 positions at the same time. [2,[19][20][21][22][23][24][25] When using the flow principle, the maximum number of positions exposed in parallel is limited to 48 samples. [21,26] To date, no exposure system has been developed to enable a sequential exposure of ALI models in a highthroughput format, such as a 96-well plate.…”

Section: Introductionmentioning

confidence: 99%

“…[ 1 ] It is apparent, not only in the field of therapy development, but also in the field of risk assessment of air pollutants – such as particulate matter, dusts, nanoparticles, and chemicals—that there is a great need for test systems that reflect the “real” situation of pollutant exposure or inhalation, both from the biological and the technical application side. [ 2 ]…”

Section: Introductionmentioning

confidence: 99%

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Development and Characterization of a 96‐Well Exposure System for Safety Assessment of Nanomaterials

Kohl

Müller

Fink³

et al. 2023

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In this study, a 96‐well exposure system for safety assessment of nanomaterials is developed and characterized using an air–liquid interface lung epithelial model. This system is designed for sequential nebulization. Distribution studies verify the reproducible distribution over all 96 wells, with lower insert‐to‐insert variability compared to non‐sequential application. With a first set of chemicals (TritonX), drugs (Bortezomib), and nanomaterials (silver nanoparticles and (non‐)fluorescent crystalline nanocellulose), sequential exposure studies are performed with human lung epithelial cells followed by quantification of the deposited mass and of cell viability. The developed exposure system offers for the first time the possibility of exposing an air–liquid interface model in a 96‐well format, resulting in high‐throughput rates, combined with the feature for sequential dosing. This exposure system allows the possibility of creating dose‐response curves resulting in the generation of more reliable cell‐based assay data for many types of applications, such as safety analysis. In addition to chemicals and drugs, nanomaterials with spherical shapes, but also morphologically more complex nanostructures can be exposed sequentially with high efficiency. This allows new perspectives on in vivo‐like and animal‐free approaches for chemical and pharmaceutical safety assessment, in line with the 3R principle of replacing and reducing animal experiments.

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“…The base module holds another insert for a 6-well QCM. The total surface area of the base being exposed to the aerosol was 190 cm 2 .…”

Section: Setup Of the 96-well Exposure System For Nebulization Of Tes...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Development and Characterization of a 96‐Well Exposure System for Safety Assessment of Nanomaterials

Kohl

Müller

Fink³

et al. 2023

Small

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In vitro tools for orally inhaled drug products—state of the art for their application in pharmaceutical research and industry and regulatory challenges

Metz

Hittinger²,

Lehr

2021

In vitro models

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The drug development process is a lengthy and expensive challenge for all involved players. Experience with the COVID-19 pandemic underlines the need for a rapid and effective approval for treatment options. As essential prerequisites for successful drug approval, a combination of high-quality studies and reliable research must be included. To this day, mainly in vivo data are requested and collected for assessing safety and efficacy and are therefore decisive for the pre-clinical evaluation of the respective drug. This review aims to summarize the current state of the art for safety and efficacy studies in pharmaceutical research and industry to address the relevant regulatory challenges and to provide an outlook on implementing more in vitro methods as alternative to animal testing. While the public demand for alternative methods is becoming louder, first examples have meanwhile found acceptance in relevant guidelines, e.g. the OECD guidelines for skin sensitizer. Besides ethically driven developments, also the rather low throughput and relatively high costs of animal experiments are forcing the industry towards the implementation of alternative methods. In this context, the development of orally inhaled drug products is particularly challenging due to the complexity of the lung as biological barrier and route of administration. The replacement of animal experiments with focus on the lungs requires special designed tools to achieve predictive data. New in vitro test systems of increasing complexity are presented in this review. Limits and advantages are discussed to provide some perspective for a future in vitro testing strategy for orally inhaled drug products. Graphical abstract

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Application of the market-ready NAVETTA electrodeposition chamber for controlled in vitro exposure with nano-scaled aerosols

Weiss,

Punz,

Van Laer

et al. 2024

Computational and Structural Biotechnology Journal

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Pulmonary in vitro instruments for the replacement of animal experiments

Cited by 7 publications

References 112 publications

Development and Characterization of a 96‐Well Exposure System for Safety Assessment of Nanomaterials

Development and Characterization of a 96‐Well Exposure System for Safety Assessment of Nanomaterials

In vitro tools for orally inhaled drug products—state of the art for their application in pharmaceutical research and industry and regulatory challenges

Application of the market-ready NAVETTA electrodeposition chamber for controlled in vitro exposure with nano-scaled aerosols

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