Nanoscience and Microsystems ETDs
Publication Date
Spring 4-15-2019
Abstract
Cystic fibrosis (CF) is the most common genetic disease resulting in the morbidity and mortality of Caucasian children and adults worldwide. Due to a genetic mutation resulting in malfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, CF patients produce highly viscous mucus in their respiratory tract. This leads to impairment of the mucociliary clearance of inhaled microbes. In addition to reduced microbial clearance, anoxic environmental conditions in the lungs promote biofilm-mode growth of the pathogenic bacterial species Pseudomonas aeruginosa. Chronic infections of P. aeruginosa begin in early childhood and typically persist until respiratory failure and death result. The average life-expectancy of CF patients is only about 40 years, with extensive treatment.
Although the introduction of inhaled antibiotics has increased the life expectancy of CF patients, the thick mucus and biofilm formation contribute to the failure of inhaled antibiotic drugs. In order to address these issues, we have synthesized and characterized nanoparticles and nanoparticle-drug conjugates for magnetic gradient guided drug delivery alone or in combination with medical magnetic hyperthermia to increase local temperature and decrease the viscosity of these layers. In the absence of the medical magnetic hyperthermia application, under static magnetic field, the NP drug conjugates may be gradient guided through the mucus and biofilm barriers to treat the P. aeruginosa infection directly. We synthesized and characterized iron oxide (magnetite) and iron nitride (martensite) nanoparticles as candidate nanomaterials for this application. We synthesized these materials, using environmentally friendly green chemistry methods, in multiple nanoscale size ranges. The NPs were synthesized using solvothermal methods, and characterized by transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDS), x-ray diffraction (XRD) and direct current (DC) and alternating current (AC) magnetometry. These nanocomposites demonstrate observable bacterial growth and biofilm inhibition even at surprisingly low (10 ng/mL) concentrations, making them ideal candidates for incorporation into a low-cost treatment regime. In vitro cytotoxicity testing of the iron oxide nanoparticles shows low, dosage dependent cytotoxicity in human lung adenocarcinoma cells, making the iron oxide nanoparticles an ideal candidate material for this application.
Keywords
cystic fibrosis, superparamagnetic iron oxide nanoparticles (SPIONS), drug delivery, Pseudomonas aeruginosa, antibiotic, antibacterial agent, nanomaterials, green chemistry
Document Type
Dissertation
Language
English
Degree Name
Nanoscience and Microsystems
Level of Degree
Doctoral
Department Name
Nanoscience and Microsystems
First Committee Member (Chair)
Marek Osinski, PhD
Second Committee Member
Erin Milligan, PhD
Third Committee Member
Pavan Muttil, PhD
Fourth Committee Member
Terefe Habteyes, PhD
Recommended Citation
Martin, Leisha M. A.. "Iron-containing Nanoparticles for the Treatment of Chrionic Biofilm Infections in Cystic Fibrosis." (2019). https://digitalrepository.unm.edu/nsms_etds/52
Included in
Bacteriology Commons, Biochemical and Biomolecular Engineering Commons, Medicinal and Pharmaceutical Chemistry Commons, Metallurgy Commons, Nanoscience and Nanotechnology Commons, Organic Chemicals Commons, Other Chemical Engineering Commons, Other Chemicals and Drugs Commons, Pathogenic Microbiology Commons, Pharmaceutics and Drug Design Commons, Polymer and Organic Materials Commons, Respiratory Tract Diseases Commons
