DOI
https://doi.org/10.25772/RJGB-ER09
Author ORCID Identifier
0000-0002-8719-6696
Defense Date
2024
Document Type
Thesis
Degree Name
Doctor of Philosophy
Department
Mechanical and Nuclear Engineering
First Advisor
Dr. P. Worth Longest
Abstract
Inhaled medications are a key treatment modality in multiple lung-related diseases and disorders. Considering children with cystic fibrosis (CF), improvements in the delivery of aerosol antibiotics have the potential to better eradicate bacterial lung infections, preserve lung function and thereby further extend lifespans and quality of life. The overall objective of this dissertation was to expand and validate CFD models for predicting the deposition of pharmaceutical aerosols throughout the airways and apply these models to understand the targeted delivery of inhaled antibiotics to children with CF. To accomplish this goal, three contributions were made. First, CFD methodologies for modeling aerosol transport in the respiratory airways were expanded through an analysis of meshing style and turbulent dispersion, which yielded improved agreement between CFD predictions of aerosol deposition and experimental data, especially in the underexplored areas of small-particle aerosols and low or transitional turbulence. Second, CFD analysis was utilized to produce correlations that characterize extrathoracic depositional losses in pediatric patients during oral and nasal administration of small-particle aerosols, again with a focus on the challenging problems of small-particle aerosols and low or transitional turbulence. Third, new developments were applied to a complete-airway modeling technique, which was previously developed by our group and is referred to as the Stochastic Individual Path (SIP) Approach. This model was then applied to explore the effects of particle size, flow rate, and hygroscopic growth on the regional deposition and concentration of an antibiotic pharmaceutical excipient enhanced growth (EEG) aerosol in the lung lining fluid of a healthy ~5-year-old subject. These contributions can collectively be used to develop pharmaceutical aerosol targeting strategies including the impact of EEG technology, which for the case of inhaled antibiotics in CF, can be used to improve the unification of antibiotic concentration in the surface liquid of the tracheobronchial airways.
Rights
© Morgan Thomas
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-8-2024