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Novel in vitro inhalation exposure system developed at the University of Salzburg

Date: 30/6/2017

In a collaboration between Paris Lodron University of Salzburg (PLUS) and the Flemish Institute for Technological Research (VITO NV), researchers have developed a novel air-liquid interface exposure system, affectionately named the NAVETTA by its creator Dr Madl, for the exposure of aerosolised engineered nanoparticles to living cells.

There is a growing consensus amongst the respiratory toxicology community that the use of traditional in vitro toxicological studies, using cells submerged in growth medium, may lack in their mimicry of the real-life exposure that takes place in the lungs. This is why numerous groups are coordinating research into the development of air-liquid interface systems, in which cells are exposed to particles in the gas phase. The NAVETTA is one of numerous air-liquid interface systems that already exist, and was designed to try and circumvent problems such as low deposition rates, and to lessen stress-related effects upon cell cultures.

The new proof-of-principle study published in Environmental Science & Technology describes a prototype system, which has since been patented by PLUS and VITO NV, with a number of features intended to enhance in vitro respiratory toxicology testing. The flatbed aerosol exposure chamber incorporates climate control features to allow comfortable maintenance of cells during the duration of an exposure period, as well as a controlled laminar air flow, which can be adjusted to replicate the breathing velocities of different lung regions. These features, and the deposition of particles onto cells directly from the gas phase, provide more realistic exposure conditions than the traditional in vitro approach, in which cells are submerged in growth medium and particles are suspended in the same media prior to exposure. In a submerged system, it’s challenging to determine if a dispersion of particles is behaving as an aerosol might be expected to, and to study what differences in behaviour may result from the distinct physicochemical characteristics of the particles in these different states. Employing techniques that offer controllable experimental conditions as close to reality as possible is clearly important in seeking to resolve these uncertainties.

There are, however, limitations to using an air-liquid interface system. It is unlikely to become a high-throughput method in the near future, and moreover, due to high surface tension at the cell layer, deposition of aerosolised particles, especially nanoparticles, is problematic. The group in Salzburg has been working on this for some time, and have previous publications optimising the technology found within the NAVETTA, which uses an electrostatic field-assisted mechanism to enhance and improve deposition.

The authors hope that this novel system will contribute the growing applications in which nanoparticle exposure is assessed in conditions that mimic those of the human lung.

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