Defense Date

Summer 6-12-2017

Availability

Immediate Access

Submission Type

dissertation

Degree Name

PhD

Department

Chemistry and Biochemistry

School

Bayer School of Natural and Environmental Sciences

Committee Chair

Ellen S. Gawalt

Committee Member

Rita Mihailescu

Committee Member

Stephanie J. Wetzel

Committee Member

Jana Patton-Vogt

Keywords

Nitric oxide, Nanoparticles, Ti-6Al-4V, PLGA, E. coli, S. epidermidis, antimicrobial, S-nitrosocysteamine, S-nitroso-penicillamine, implant

Abstract

Current methods for the treatment of bacterial infection involve the use of systemic antibiotics, which are high concentrations of antibiotics delivered over a long period time. Unfortunately, the use of systemic antibiotics can cause harmful side effects to the patient and increases the possibility for antibiotic resistance. The delivery of antibiotics or alternative antimicrobial compounds, such as nitric oxide, directly to the site of infection would decrease the amount of antibiotic necessary to treat a bacterial infection.

Poly (lactic-co-glycolic acid)/polyvinyl alcohol nanoparticles and a titanium- aluminum-vanadium metal oxide alloy implant were surface functionalized to deliver nitric oxide. Polymer nanoparticles can be used to deliver nitric oxide to patients with extensive bacterial infection in the lung, while the modified metallic implant can be used to prevent bacterial cell adhesion onto the surface post implantation. These surfaces were covalently modified with S-nitrosothiols, and characterized using infrared and ultraviolet- visible spectroscopic techniques. The attachment of the S-nitrosothiol to the nanoparticle surface resulted in a nmole of nitric oxide per milligram of nanoparticles release under physiological conditions, while the modified titanium alloy released a nmole of nitric oxide per cubic centimeter. The low concentration of nitric oxide released from the nanoparticle and titanium alloy surfaces reduced Escherichia coli growth, indicating that S-nitrosothiol remains active against bacteria after covalent immobilization to the surface. The S-nitrosothiol modified titanium alloy inhibited Staphylococcus epidermidis growth, indicating effectiveness against a gram-positive microbe. Combining both nitric oxide releasing materials with tetracycline, a commonly prescribed antibiotic, increased the effectiveness of the antibiotic, which allows for lower doses of antibiotics to be used. Thus, the polymer nanoparticles and titanium alloy developed here have the capability of delivering an antibiotic alternative, nitric oxide, directly to the site of an infection, reducing the need for harmful systemic antibiotics and the possibility of antibiotic resistance.

Language

English

Additional Citations

Reger, Nina A., Wilson S. Meng, and Ellen S. Gawalt. "Surface modification of PLGA nanoparticles to deliver nitric oxide to inhibit Escherichia coli growth." Applied Surface Science 401 (2017): 162-171.

Reger, Nina A., Wilson S. Meng, and Ellen S. Gawalt. "Antimicrobial Activity of Nitric Oxide-Releasing Ti-6Al-4V Metal Oxide." Journal of Functional Biomaterials 8.2 (2017): 20.

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