Numerical Studies of Nanoparticle Transport and Deposition in Terminal Alveolar Models with Varying Complexities

Abstract

Background: The integration of inhalation drug delivery and nanotechnology offers exciting potentials to enhance the targeting, release, diagnostic, and therapeutic outcomes of drugs. Human lungs provide many advantages over other routers such as noninvasive delivery, a large surface area for absorption, avoiding the first-pass metabolism, and quick therapeutic onset. It is crucial to understand nanoparticle dosimetry in the acinar region to reliably evaluate the therapeutic outcomes of nanomedicines. However, an acinus unit comprises up to 10,000 alveoli and to model a complete acinus is still a prohibitive task. Besides, the presence of inter-alveolar septa creates a labyrinth pathway for inhaled airflow and particles. Methods: The objective of this study is to numerically investigate nanoparticle deposition in three alveolar models with varying physical complexities, which retain 1, 4, and 45 alveoli, respectively. A discrete-phase Lagrangian model was implemented to track nanoparticle trajectories under the influence of rhythmic wall expansion and contraction. Both temporal and spatial dosimetry in the alveoli were computed. Results: Strikingly different behaviors were observed in the dynamic alveolar model between micron particles and nanoparticles. Minimal deposition rates were predicted for 500–600 nm particles for all the three models considered. Consistently lower deposition rates were found in the 45-alveoli model than the other two simplified models for all particles ranging from 1 nm to 1000 nm. Considering the gravitational orientation effect, nanoparticles smaller than 200 nm appears insensitive to the alveolar orientation and only becomes perceivable around 500 nm. For nanoparticles larger than 500 nm, lower doses were predicted in the horizontal alveoli than in the vertical alveoli, regardless of the model complexity. Conclusions: The magnitude of the airflow velocity (depending on ventilated volume) is an essential factor in determining the deposition of inhaled nanoparticles. Future correlation development for acinar deposition should consider the velocity distribution in different regions of the acinus.