Defense Date

2024

Document Type

Thesis

Degree Name

Master of Science

Department

Biomedical Engineering

First Advisor

Rebecca Heise

Second Advisor

Masahiro Sakagami

Third Advisor

Christopher Lemmon

Abstract

Cystic fibrosis (CF) is a progressive genetic disorder that affects around 40,000 people in the United States. CF is characterized by a mutation in the CFTR protein that causes dysregulated ion transport across epithelial cells, producing viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in CF patients that are resistant to antibiotics. One antibiotic approved to treat these infections is levofloxacin (LVX) that functions to inhibit bacterial replication, but can be further developed into tailorable particles. Nanoparticles are an emerging inhaled therapeutic made for enhanced targeting and delivery to specific lung structures. Previously, porcine lung extracellular matrix (PL-ECM) nanoparticles (NPs) have demonstrated pro-regenerative and non-toxic effects in vitro, capable of targeting the lower respiratory tract. However, CF mucus presents a barrier to inhaled therapeutics by size and interaction filtering. We hypothesize that the combination of LVX with PL-ECM, formed into nanoparticles with suitable size and charge, will be able to target CF bacterial infections by penetrating through the mucus. Two hybrid formulations of a 10:1 and 1:1 ratio of LVX to ECM have shown neutral surface charges and an average size of ~525 nm and ~300 nm, respectively. The NPs have also shown the ability to penetrate through CF mucus and slowed drug dissolution. The NPs have also shown to be non-toxic to human airway epithelial cells and are effective in inhibiting P. aeruginosa and S. aureus.

Rights

© Raahi Patel

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-8-2024

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