Nanoparticle Mass Transfer From Lung Airways to Systemic Regions—Part I: Whole Lung Aerosol Dynamics

Abstract

This is a twopart paper describing inhaled nanoparticle (NP) transport and deposition in a model of a human respiratory tract (Part I) as well as NPmass transfer across barriers into systemic regions (Part II). Specifically, combining highresolution computer simulation results of inhaled NP deposition in the human airways (Part I) with a multicompartmental model for NPmass transfer (Part II) allows for the prediction of temporal NP accumulation in the blood and lymphatic systems as well as in organs. An understanding of nanoparticle transport and deposition in human respiratory airways is of great importance, as exposure to nanomaterial has been found to cause serious lung diseases, while the use of nanodrugs may have superior therapeutic effects. In Part I, the fluidparticle dynamics of a dilute NP suspension was simulated for the entire respiratory tract, assuming steady inhalation and planar airways. Thus, a realistic airway configuration was considered from nose/mouth to generation 3, and then an idealized triplebifurcation unit was repeated in series and parallel to cover the remaining generations. Using the current model, the deposition of NPs in distinct regions of the lung, namely extrathoracic, bronchial, bronchiolar, and alveolar, was calculated. The regionspecific NPdeposition results for the human lung model were used in Part II to determine the multicompartmental model parameters from experimental retention and clearance data in human lungs. The quantitative, experimentally validated results are useful in diverse fields, such as toxicology for exposurerisk analysis of ubiquitous nanomaterial as well as in pharmacology for nanodrug development and targeting.