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

Inhaled therapy has\nbecome a crucial treatment option for respiratory\ndiseases like asthma, cystic fibrosis, and chronic obstructive pulmonary\ndisease (COPD), delivering drugs directly to bronchial and alveolar\ntissues. However, traditional static <i>in vitro</i> cell\nmodels, while valuable for studying pharmacokinetics (PK) and pharmacodynamics\n(PD), fall short in replicating the dynamic nature of physiological\nbreathing. In this study, we present a breathing lung chip model that\nintegrates a dynamic breathing mechanism with an air–liquid\ninterface (ALI) culture environment to overcome these limitations.\nThe platform replicates key aspects of lung physiology, including\na functional airway interface, cyclic breathing motion, and medium\ncirculation. Using the Calu-3 cell line to model airway epithelium,\nour experiments show that the incorporation of breathing motion significantly\nenhances the efficacy of inhaled drug delivery and cellular uptake,\nresulting in improved treatment outcomes compared to direct exposure\nof the drug. While further research is needed to explore its full\npotential, this platform holds promise for advancing inhaled drug\nscreening and respiratory disease research.