Document Type

Thesis - Open Access

Award Date

2026

Degree Name

Master of Science (MS)

Department / School

Mechanical Engineering

First Advisor

Basu Saikat

Abstract

The nasopharynx, the upper part of the pharynx located at the back of the nose serves as a critical hotspot for initial respiratory infections via inhaled transmission, largely due to the presence of specific surface receptors that pathogens can exploit for cell invasion, combined with a relatively sparse local mucociliary substrate. To enhance the therapeutic efficacy against certain pathogens, such as the SARS and Influenza viruses, it is therefore essential to improve the targeted delivery of drugs to the nasopharynx. This study explores the use of intranasal sprays as a method for drug administration and models the transport of sprayed drug particulates during relaxed inhalation, through experimentally validated simulations of the relevant respiratory flow physics inside anatomical domains built from medical imaging. We derive the nasopharyngeal deposition efficiency (ξ, in %) across a broad range of formulation and device parameters, including the material density of the sprayed formulation (ρ, in g/ml), particulate sizes (d, in μm), and the plume angle of the conical spray discharge (θ, in degrees). The key takeaway from our study will address the following question: What specific combination of ρ, d, and θ will maximize sprayed drug delivery to the nasopharynx? Improving the efficacy of nasal sprays by enhancing targeted drug delivery to intra airway tissue sites prone to infection onset is hypothesized to be achievable through an optimization of key device and formulation parameters, such as the sprayed droplet sizes, the spray cone angle, and the formulation density. This study focuses on the nasopharynx, a primary locus of early viral entry, as the optimal target for intranasal drug delivery. Three-dimensional anatomical upper airway geometries reconstructed from high-resolution computed tomography scans were used to numerically evaluate a cone injection approach, with inert particles mimicking the motion of sprayed droplets within an underlying inhaled airflow field. We have considered monodisperse sprayed particles sized between 10-50 μm, six densities ranging from 1.0-1.5 g/ml for the constituent formulation, and twelve plume angles spanning 15◦ - 70◦ subtended by the spray jet at the nozzle position. Large Eddy Simulation-based modeling of the inhaled airflow physics within the anatomical domains was coupled with a Lagrangian particle-tracking framework to derive the drug deposition trend at the nasopharynx. The resulting three-dimensional deposition contour map, obtained by interpolating the outcomes for the discrete test parameters, revealed that nasopharyngeal deposition peaked for droplet sizes 25-45 μm and plume angles ≤ 30◦, when the nasopharyngeal deposition rates are averaged over the test airway geometries and formulation densities. In addition, the formulation density of 1.0 g/ml yielded the highest mean deposition rate, over the tested range of sprayed particle sizes and plume angles. The findings were experimentally validated through representative physical spray tests conducted in a 3D-printed replica of one of the test geometries and collectively demonstrate that rational optimization of the intranasal spray design is attainable, with substantial enhancement of targeted drug delivery to the nasopharynx.

Publisher

South Dakota State University

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Rights Statement

In Copyright