80 Testing respiratory effects and immunotoxic impacts employing the NAVETTA <i>in vitro</i> aerosol exposure system

Abstract Exposure of lung epithelia to environmental airborne agents causing inflammation is omnipresent. With growing efforts in lung disease prevention and treatment, reduction of exposure levels and pulmonary drug delivery are gaining interest. Following the 3R principles , in vitro air-liquid interface (ALI) cultures mimicking aerosol deposition on lung tissue has potential for risk assessment, since it provides both dose and hazard information for a given exposure scenario. We have developed a flatbed in vitro aerosol exposure chamber, termed NAVETTA, which operates on the ALI and allows for immunotoxicity studies establishing a reliable, reproducible, and efficient system that mimics the deposition of inhaled aerosols in different parts of human lung. It operates at low lateral airflow enabling efficient deposition of gently aerosolized substances while providing an electric field. Employing lung deposition modelling informs on the delivery ratios to the different areas of the human respiratory system. In line with the Safe-and-Sustainable-by-Design (SSbD) concept for innovation in advanced materials and chemicals the NAVETTA can be employed for Tier 3 level hazard assessment for diverse inhalant substances relevant for environmental or occupational exposure scenarios or for studying the interaction of allergens with nanomaterials at molecular and cellular levels. Such investigations have given rise to deeper understanding of mechanisms underlying adverse outcome pathways. Moreover, NAVETTA has proven useful for pharmaceutical efficacy testing capable of monitoring the downregulating effects of anti-inflammatory drugs delivered via aerosols from various states, including dry powder, liquid suspension, or being packaged into nanomedical carrier systems.