Inhalable Mucociliary-On-Chip System Revealing Pulmonary Clearance Dynamics in Nanodrug Delivery

Abstract

The development of a inhaled nanodrug delivery assessment platform is crucial for advancing treatments for chronic lung diseases. Traditional in vitro models and commercial aerosol systems fail to accurately simulate the complex human respiratory patterns and mucosal barriers. To address this, we have developed the breathing mucociliary-on-a-chip (BMC) platform, which replicates mucociliary clearance and respiratory dynamics in vitro. This platform allows for precise analysis of drug deposition and penetration, providing critical insights into how liposomes and other nanocarriers interact with lung tissues under various airflow conditions. Our results reveal that liposomes penetrate deeper into the cellular layer under high shear stress, with both static and dynamic airflows distinctly affecting their drug release rates. The BMC platform integrates dynamic inhalation systems with mucociliary clearance functionality, enabling a comprehensive evaluation of drug delivery efficacy. This approach highlights the importance of airflow dynamics in optimizing inhalable nanodrug delivery systems, improving nanocarrier design, and tailoring drug dosages and release strategies. The BMC platform represents a significant advancement in the field of inhaled nanodrug delivery, offering a more accurate and reliable method for assessing the performance of therapies. By providing a detailed understanding of drug interactions with lung tissues, this platform supports the development of personalized inhaled therapies and offers promising strategies for treating pulmonary diseases and advancing nanodrug development.