Document Type

Thesis - Open Access

Award Date

2024

Degree Name

Master of Science (MS)

Department / School

Mechanical Engineering

First Advisor

Saikat Basu

Abstract

This thesis aims to explore efficient drug delivery to clinical target sites along the human upper airway that strongly depends on variables associated with the delivery device and the drug formulation, e.g., the device plume angle, particle sizes of drug solution, drug delivery speed of the device, viscosity of the drug solution, delivery axis orientation, and the formulation density. In our investigation, we prioritize the nasopharynx, the primary site of initial viral infection, as the ideal target zone for drug delivery. We have used Large Eddy Simulation and Lagrangian techniques to replicate breathing at 15 L/min and quantify regional drug deposition; the latter as a function of the device plume angle and the formulation material density, fixing other variables. Two anatomic nasal geometries are being studied with conically injected spray droplet sizes of 10–50 μm, while the formulation density varies between 1100-1500 kg/m3, and the plume angles are 15◦-70◦. The results comprise novel 3D surface maps (for each formulation density) with plume angles and particle sizes along the horizontal plane and regional deposition (at the nasopharynx) along the vertical axis. Findings show that nasopharyngeal deposition peaks for particle diameters 11-22.5 μm for plume angles < 50◦. Next focusing on an interactive digital interface development based on particle transport data obtained from computational fluid dynamics (CFD) simulations from the previous study. The interface will utilize our computational fluid dynamics (CFD) data library, along with an interpolation/extrapolation algorithm, to promptly estimate the efficiency of drug delivery to specific tissue regions. This projection will be based on a diverse range of drug and formulation characteristics, which will be inputted by the end-user. These characteristics include particle sizes and their distribution, spray plume geometry, formulation density, and viscosity. The simulations conducted in the back end will include the necessary data architecture of the digital interface, including a wide variety of therapeutic formulation and delivery device characteristics that are considered practical and controllable. Subsequently, We have performed physical spray tests to experimentally evaluate drug penetration to the nasopharynx (a key target site for viral infections) for two different nozzle placements – one for current package instructions coming with over-the-counter spray products and the other for the spray usage procedure with the proposed nozzle placement angle (namely, 12-15°) to enhance targeted drug delivery. Then the next study delves deeper into airborne pathogen transmission, emphasizing the expulsion and spread of respiratory particles. It particularly addresses the overlooked aspect of fluid dynamics in navigating virus-carrying particles through the respiratory tract to susceptible upper airway regions. Utilizing a detailed multi-scale modeling strategy, underscored by Large Eddy Simulations of airflow and particle paths within realistic airway models from CT scans, it showcases smallpox as an example. By merging fluid dynamics outcomes with virological and epidemiological data on smallpox, it accurately defines the infectious dose range (of the order of O(2), or more precisely 1 to 180.), demonstrating the approach’s precision in aligning with established smallpox virological parameters. The thesis additionally investigates airflow dynamics in a well-ventilated classroom situated in a tropical environment, aiming to comprehend how respiratory particles disperse in closed settings. It examines the influence of the emitter’s location within the classroom on the distribution of exhaled, potentially virus-bearing droplets across the space. Findings indicate that the further the emitter is from the ventilation outlet, the greater the dispersion and mixing of exhaled breath, thereby increasing the likelihood of disease transmission among occupants.

Publisher

South Dakota State University

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