Parametric Optimization of an Air–Liquid Interface System for Flow-Through Inhalation Exposure to Nanoparticles: Assessing Dosimetry and Intracellular Uptake of CeO2 Nanoparticles

Abstract

Air-liquid interface (ALI) systems have been widely used in recent years to investigate the inhalation toxicity of many gaseous compounds, chemicals, and nanomaterials and represent an emerging and promising <i>in vitro</i> method to supplement <i>in vivo</i> studies. ALI exposure reflects the physiological conditions of the deep lung more closely to subacute <i>in vivo</i> inhalation scenarios compared to submerged exposure. The comparability of the toxicological results obtained from <i>in vivo</i> and <i>in vitro</i> inhalation data is still challenging. The robustness of ALI exposure scenarios is not yet well understood, but critical for the potential standardization of these methods. We report a cause-and-effect (C&E) analysis of a flow through ALI exposure system. The influence of five different instrumental and physiological parameters affecting cell viability and exposure parameters of a human lung cell line <i>in vitro</i> (exposure duration, relative humidity, temperature, CO₂ concentration and flow rate) was investigated. After exposing lung epithelia cells to a CeO₂ nanoparticle (NP) aerosol, intracellular CeO₂ concentrations reached values similar to those found in a recent subacute rat inhalation study <i>in vivo</i>. This is the first study showing that the NP concentration reached <i>in vitro</i> using a flow through ALI system were the same as those in an <i>in vivo</i> study.