Description
- Abstract:
- Antibiotic resistance and the lack of new antimicrobial therapies create significant challenges for the treatment of infections. Therefore, there is an urgent clinical need to develop novel treatments targeting bacterial biofilms to reduce the risk of infection, without resorting to antibiotics. The goal of this thesis is, for the first time, to integrate two novel approaches, i.e. nanotechnology and metabolic stimulation, to eradicate antibiotic-resistant biofilms. The metabolic microenvironment of the biofilms has been manipulated to improve the antibacterial properties of superparamagnetic iron oxide nanoparticles (SPION) as well as nanorough device surfaces. First, it has been shown that engineered nanoscale topographies provide surfaces that are more resistant to bacterial growth than conventional polyvinyl chloride (PVC). In addition, for the first time, the presence of fructose on the nanorough PVC further decreased the planktonic S. aureus growth and biofilm formation, without use of any antibiotics. Moreover, a simple, broad-spectrum and low-cost dual-sided approach which uses SPION in combination with metabolites (i.e., fructose, glucose, and mannitol) has been developed as an alternative to existing antibacterial strategies. This strategy offers further improved efficacy of SPION against persistent gram-positive and gram-negative bacteria infections by manipulating the biofilm metabolic microenvironment, creating a new nanotechnology-driven approach. Further, biofilm eradication by the engineered SPION was significantly better than vancomycin, the antibiotic of last resort. In addition, it has been demonstrated that SPION conjugated with antibacterial silver salts exhibit strong eradication properties against the antibiotic-resistant (MRSA) biofilms. Antibacterial properties of silver-conjugated SPION were further improved when an external magnetic field was applied as their magnetic core enabled them to penetrate into the biofilms. This thesis, for the first time, highlighted the importance of biofilm metabolic microenvironment for the nanotechnology-driven approaches. It is envisioned that these simple and inexpensive approaches could lead to novel alternative treatments to the only current clinical option, vancomycin, which MRSA has started to develop a resistance towards. These novel nanotechnology-driven approaches can lead to successful clinical outcomes in terms of minimizing infections, longer medical device lifetimes, and decreasing antibiotic usage.
- Notes:
- Thesis (Ph.D. -- Brown University (2013)
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Citation
Durmus, Naside Gozde,
"Enhanced Efficacy of Nanotechnology-Driven Approaches against Antibiotic-Resistant Biofilms in the Presence of Metabolites"
(2013).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z03R0R6C
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....