Date of Award

8-2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioengineering

Committee Member

Dr. Narendra Vyavahare, Ph.D, Committee Chair

Committee Member

Dr. Jeoung Soo Lee, Ph.D

Committee Member

Dr. Alexey Vertegel, Ph.D

Committee Member

Dr. Renee J. LeClair, Ph.D

Abstract

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in U.S. following cancer and heart disease. COPD is an umbrella term for two chronic pathological conditions, namely chronic bronchitis and emphysema that are seen in patients. According to American Lung Association, 12.7 million Americans have been diagnosed with COPD, while 24 million people have impaired lung function, considered as underdiagnosed for the disease resulting in a huge cost to the nation of about $50 billion. Emphysema is an airway disease in which inflammation mediated elastin damage occurs over a long period. Owing to protease/ anti-protease imbalance because of this chronic inflammation, various "elastases" can degrade elastin. Loss of elastin in the lungs has been shown to correlate with loss of lung function in patients. Currently available treatments for COPD aim at only providing temporary relief to the patients by mitigating inflammation or by the action of bronchodilators. Elastin breakdown and chronic inflammatory conditions are hallmark of emphysema. We have developed unique way to deliver nanoparticles tagged with elastin antibody that recognizes degraded elastin in the cardiovascular disease sites. In this research, we have shown that this targeted delivery can be extended to emphysematous lungs to deliver doxycycline and pentagalloyl glucose (PGG) in an attempt to inhibit matrix metalloproteinase (MMP) activity and to preserve elastin in the lung tissue using both in vitro and in vivo approaches.

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