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Acini-on-Chip: Novel In Vitro Assessment of Particle Dynamics and Deposition in the Deep Lungs

Fishler R, Sznitman J.

RDD Europe 2017. Volume 1, 2017: 119-128.

Abstract:

The current paradigm for designing therapeutic inhalation aerosol products revolves around attempting to optimize deposited drug dose based on in vitro measurement of aerodynamic particle size distributions (e.g., using cascade impactors) from developmental formulations and devices. This approach is known to yield inhalation products with high inter-subject variability as judged by in vivo experiments using radiolabeled particles. Historically, in vivo experiments were not conducted routinely during early product development because they are too cost- and labor-intensive. Furthermore, current in vivo experiments lack the spatial and temporal resolution necessary to characterize detailed aerosol dynamics and deposition patterns. With the advent of microfabrication and 3D printing techniques, particle deposition assays using in vitro airway models are gaining attraction by offering cheaper yet potentially accurate deposition estimates. Here, we discuss recent developments in microfluidic alveolated airway trees capturing anatomical scales, breathing motions and physiological air flow patterns. These acini-on-chip allow, for the first time, direct quantification of aerosol transport and deposition patterns expected in the deep lung. Despite challenges in capturing faithfully the innate respiratory environment, such advancements are anticipated to pave the way towards accurate and reliable in vitro lung models for aerosol assays that may someday replace pre-clinical studies.