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Modeling aerosol dynamics in the airways is challenging, and most modern personalized in vitro tools consider only a single inhalation maneuver through less than 10% of the total lung volume. Here, we present an in vitro modeling pipeline to produce a device that preserves patient-specific upper airways while approximating deeper airways, capable of achieving total lung volumes over 7 liters. The modular system, called TIDAL, includes tunable inhalation and exhalation breathing capabilities with resting flow rates up to 30 liters per minute. We show that the TIDAL system is easily coupled with industrially and clinically relevant devices for aerosol therapeutics. Using a vibrating mesh nebulizer, we report central-to-peripheral (C:P) aerosol deposition measurements aligned with both in vivo and in silico benchmarks. These findings underscore the effectiveness of the TIDAL model in predicting airway deposition dynamics for inhalable therapeutics. 

There is nothing like a global pandemic to motivate the need for improved respiratory treatments and mucosal vaccines. Stimulated by the COVID-19 pandemic, pulmonary aerosol drug delivery has seen a flourish of activity, building on the prior decades of innovation in particle engineering, inhaler device technologies, and clinical understanding. As such, the field has expanded into new directions and is working toward the efficient delivery of increasingly complex cargos to address a wider range of respiratory diseases. This review seeks to highlight recent innovations in approaches to personalize inhalation drug delivery, deliver complex cargos, and diversify the targets treated and prevented through pulmonary drug delivery. We aim to inform readers of the emerging efforts within the field and predict where future breakthroughs are expected to impact the treatment of respiratory diseases. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 26 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.