Realistic Exposure Methods for Investigating the Interaction of Nanoparticles with the Lung at the Air-Liquid Interface In Vitro

In light of the increasingly abundant use of engineered nanoparticles (NPs) and the ongoing exposure to ambient ultrafine particles it is imperative that the potential for NPs to elicit adverse effects on human health is understood. In order to determine the potential harm that NPs may exert, many different in vitro systems have been used. Commonly in vitro nanotoxicology studies use NP suspensions applied directly to cell cultures. Although the use of in vitro monoculture systems to assess the effects of NPs on, for example, the lung is frequently debated, the use of suspension exposures is not realistic in relation to the exposure of NPs to humans via inhalation; the primary exposure route to the human body for NPs. As an alternative to the suspension (or submerged) exposure method, numerous different exposure systems at the air-liquid interface have been developed and used in nanotoxicology research, which mimic the realistic conditions of NP inhalation exposure. In addition, such air-liquid exposure systems also offer the advantage to determine the exact dose (or concentration) which is deposited on the cell surface. The aim of this review is to provide a description of these different exposure systems, to explain how they recreate realistic inhalation conditions for occupational and environmental exposure, as well to describe how they may be used to gain an insight into how NPs may interact with the epithelial airway barrier following inhalation.