Document Type

Dissertation - Open Access

Award Date

2023

Degree Name

Master of Science (MS)

Department / School

Mechanical Engineering

First Advisor

Saikat Basu

Keywords

Computational Fluid Dynamics, Nasal drug delivery, Nasopharyngeal bolus, Numerical modeling, Public health, Respiratory transport

Abstract

This thesis aims to explore the potential of improving the efficacy of drugs for treatment of viral infections by targeting the nasopharynx, which is commonly the first site of infection for many viral pathogens. Currently, intranasal sprays are used, but the standard protocol (“Current Use” or CU) results in suboptimal drug deposition at the nasopharynx. To address this issue, an “Improved Use” or, IU protocol has been proposed, which involves pointing the spray bottle at a shallower angle and aiming slightly towards the cheeks. The IU delivery is also robust to perturbations in spray direction, which highlights the practical utility of this new drug administration protocol. The results of the simulation are experimentally verified using a 3D-printed airway cavity of a different subject. Next with the smallpox virus as an example pathogen, a numerical modeling framework for airborne respiratory diseases has been made. This modeling framework shows that the regional deposition of virus-laden inhaled droplets at the initial infection site (for smallpox, this is the oropharynx and the lungs) peaks for the droplet size range (8–27 μm for oropharyngeal deposition, and ≤ 14 μm for lungs) and can be used to determine the number of virions required to launch the infection in a subject. Subsequently, to explore the mechanics of lower airway disease progression, we have considered SARS-CoV-2. We have investigated the spread of SARS-CoV-2 from the nasopharynx to the lower airway. Using computational models, the inhalation process has been tracked with quantification for the volume of nasopharyngeal liquid transmitted to the lower airspace during each aspiration. The results suggest that a significant amount of liquid may be aspirated each day, which could lead to an increased risk of aggressive and accelerated lung infections in individuals with conditions like dysphagia. Finally, in view of the high cost and time required for conducting numerous numerical simulations, we have checked Machine Learning platforms as an alternative method for predicting regional deposition at various anatomical regions based on the geometric features of the anatomic flow domains in respiratory physiology. As an ancillary topic, the thesis also explores the morphological characteristics of the nose and their influence on airflow patterns and heat transfer dynamics inside the nasal cavity of a pig’s nose. The findings indicate that tortuosity has a crucial role in particle capture efficiency, particularly in high-olfactory mammalian species such as pigs and opossums. Understanding the fluid-particle interactions in nasal cavities could lead to the development of nature-inspired designs for various engineering processes, such as the creation of novel filtration devices. Therefore, it is essential to continue investigating the significance of heat management and particle screening in nasal structures to reveal their mechanistic functions and translate this information into practical applications.

Library of Congress Subject Headings

Drug targeting.
Nasopharynx.
Respiratory infections.
Virus diseases.
Drug delivery systems.

Publisher

South Dakota State University

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Rights Statement

In Copyright