Development of alveoli-distributed lung geometries for humans and rats to predict localized particle deposition in the respiratory tract

Abstract

Inhalation drug delivery has gained considerable attention due to its rapid onset and the potential for optimized delivery, minimizing or eliminating adverse side effects. The delivery targets can be local (such as the respiratory tract) or systemic. Extensive research has been conducted on the deposition of inhaled particles in the lungs, with available models relying on simplifying assumptions. However, these models require improvements to more accurately predict site-specific deposition patterns. In this study, we combined morphometric data for the conducting airways in humans and Sprague Dawley rats with additional data on the distribution and number of respiratory units in both species. This enabled us to create a new generation of 2-path and lobar-specific, 2-path lung geometries. Unlike previous models, which separated the conducting and respiratory airways at a preassigned generation number, our proposed geometries integrated these pathways, assigning alveolar units to the conducting airways where data supported it. A particle deposition model based on these updated geometries was developed to predict both local and regional deposition. While the regional deposition results were consistent with previous studies, the local (site-specific) deposition predictions differed significantly, offering more realistic predictions due to the conducting-alveolar airway structure that mimics geometric realism. These new geometries are recommended for applications that require accurate assessment of local deposition, such as targeted drug delivery.