DOI
https://doi.org/10.25772/0SPZ-KR29
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