A Dynamic Breathing Lung Chip for Precise Evaluation of Inhaled Drug Efficacy and Airway Epithelial Responses

Inhaled therapy has become a crucial treatment option for respiratory diseases like asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD), delivering drugs directly to bronchial and alveolar tissues. However, traditional static <i>in vitro</i> cell models, while valuable for studying pharmacokinetics (PK) and pharmacodynamics (PD), fall short in replicating the dynamic nature of physiological breathing. In this study, we present a breathing lung chip model that integrates a dynamic breathing mechanism with an air-liquid interface (ALI) culture environment to overcome these limitations. The platform replicates key aspects of lung physiology, including a functional airway interface, cyclic breathing motion, and medium circulation. Using the Calu-3 cell line to model airway epithelium, our experiments show that the incorporation of breathing motion significantly enhances the efficacy of inhaled drug delivery and cellular uptake, resulting in improved treatment outcomes compared to direct exposure of the drug. While further research is needed to explore its full potential, this platform holds promise for advancing inhaled drug screening and respiratory disease research.