Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of death worldwide. Alveolar wall destruction is a significant contributor to COPD. Inflammatory macrophages are a major source of the Extracellular Matrix (ECM) proteolysis. ECM breakdown causes air to get trapped in the alveoli, obstructing airflow. One step in curing COPD may be to convert inflammatory to pro-regenerative macrophages. Recently, decellularized ECM scaffolds have shown the ability to induce a pro-regenerative phenotype.
Yet these scaffolds are incapable for reaching the alveolar region of the lungs. To reach the alveolar region particles need a diameter of 1-5 μm or smaller than 300 nm. We used protein from decellularized lung tissue to create nanoparticles. By first digesting the protein in acid, we electrosprayed the solution into nanoparticles. The average size of the nanoparticles is 225 (± 67) nm, within the requirements to reach alveoli. However, another barrier exists for treating this disease. That barrier is mucus; mucus hypersecretion is another sign of COPD. The formed particles are capable of penetrating the mucus layer in COPD. After characterizing the particles, we began in vitro investigations. First, we measured cytotoxicity of the nanoparticles. In alveolar epithelial cells, adding nanoparticles to the media increased cellular proliferation. We then added the nanoparticles to isolated murine macrophages. The nanoparticles induced a pro-regenerative phenotypic shift in murine macrophages. These experiments reveal that these nanoparticles may become an effective treatment for degenerative lungs diseases, such as COPD, after further investigation.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-6253 |
| Date | 01 January 2017 |
| Creators | Link, Patrick |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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