Author ORCID Identifier

Defense Date


Document Type


Degree Name

Doctor of Philosophy


Mechanical and Nuclear Engineering

First Advisor

Dr. Laleh Golshahi


The popularity of pulmonary aerosol delivery is increasing due to numerous advantages including non-invasiveness, fast onset of action, avoidance of the first-pass metabolism, and relatively good patient compliance. However, aerosol delivery to the site of action within the extrathoracic regions is challenging to quantify from a regulatory perspective due to the combined effects of the device and formulation characteristics, complex morphology of the airways resulting in extreme anatomical variabilities, and user dependent administration methods. Besides the therapeutic aerosol delivery, electronic nicotine delivery systems (ENDS) are a user-driven aerosol technology used to deliver nicotine as one of the electronic liquid (e-liquid) constituents in a dense aerosol cloud. Given the dramatically increasing prevalence of the ENDS, diverse variety of products, and lack of regulation due to the discrepancies in current data, a systematic in vitro study was found needed to better understand the thoracic nicotine delivery and provide a platform for future in vivo studies and potential in vitro in vivo correlations (IVIVC).

Aim 1 of this study was to investigate the challenges of delivering aerosol with locally-acting metered-dose nasal sprays, MAD atomizer, and two nebulizers, to their sites of action in three anatomically-correct healthy airway models which were cohort representative of the adult, child, and toddler anatomy. The study identified significantly lower regional deposition patterns in two pediatric subjects versus the adult, underlining that anatomical variabilities and user-dependent administration parameters are not considered in a majority of current therapeutic aerosol delivery devices, commercialized for children.

Aim 2 focused on improving technical capabilities, including realistic characterization of nasal sprays and simulating individual testing protocol for each user based on their anatomy. Twenty subjects as a representative cohort of adult population were considered. Device and anatomy-dependent parameters including head angle, nasal inhalation flow rate, and spray actuation force-time profile, were kept controlled to simulate a realistic and repeatable in vitro test method. Following the in vitro quantification of the deposition patterns, the relationships between current bioequivalence in vitro spray characterization test metrics and nasal deposition patterns, and primary anatomical characteristics responsible for the regional deposition were explored. Along with developing the in vitro models, the importance of identification of the internal nasal valve (INV), which is known as the plane separating the anterior and posterior regions was realized. The existing radiographical assessment methods of INV were found controversial. Therefore, a novel methodology was developed and optimized for INV assessment before sectioning the digital STL airway geometries to anterior and posterior regions.

Aim 3 was on designing a gas-assisted aerosol delivery system, mainly to the paranasal regions, while taking advantage of the influential factors identified in Aim 1. A systematic study was designed to investigate the effect of gas properties and bidirectional administration technique, while providing a design feature to aim aerosol to the inferior, middle, and superior turbinates using different gas flow rates. Modified nasal adapters with controlled insertion angles significantly improved the paranasal delivery dose. Using a proper design with controlled insertions and aiming the aerosol to the superior turbinates, significantly improved the paranasal deposition patterns.

Aim 4 was to characterize the physical characteristics of the aerosol emitted from a common ENDS product filled with multiple customized e-liquid formulations and commercialized e-liquids, and compare their deposition in an in vitro mouth-throat model of an adult subject. The model was modified to capture the intrathoracic dose (aerosol deposited onto the filter when leaving the throat), exhaled dose, and the retained dose in the model. The effects of influential parameters on ENDS post-vaporized nicotine delivery and extrathoracic loss of inhaled aerosol were explored. These parameters were the ENDS atomizing wattage, puff flow rate, and e-liquid composition in terms of PG:VG ratio, and nicotine form. Deposition patterns confirmed higher thoracic doses using the e-liquids with protonated nicotine form versus the free-base, which could be explained considering the innate characteristics of protonated nicotine, mainly being less volatile compared to the other forms.


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Available for download on Tuesday, April 28, 2026