Overcoming pathogenic biofilm recalcitrance with magnetic mitigation therapies

Date

2019-05

Authors

Heersema, Lara Ashley

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Abstract

Pathogenic biofilms are associated with the chronicity of infectious diseases and are difficult to treat using current therapies. Biofilm recalcitrance enables antibiotic resistance up to 1,000 fold compared to non-biofilm related infections and requires longer treatment regimens. This increase in the use of antimicrobials in the fight against biofilms contributes to the alarming increase in antibiotic resistant microorganisms globally. Therefore, there is a need for new treatments that are effective against multiple types of pathogenic biofilms, can target biofilms in surface and deep tissues, exhibit low or no toxicity, and can synergize with current pharmacological therapies without inducing resistance. Towards achieving efficient biofilm disruption and removal, I report on the use of magnetic nanoparticle and magnetic field treatments optimized with current therapeutics against pathogenic biofilms. The first section of this dissertation focuses on the use and characterization of in vitro pathogenic biofilm models for susceptibility testing. Reported here is the development and characterization or a novel high-throughput multispecies oral caries associated biofilm model. This model was designed to facilitate screening of novel therapies against a relevant oral caries model with both commensal and pathogenic microorganisms. The second section of this dissertation focuses on the use of magnetic nanoparticles and magnetic fields to mechanochemically disrupt and remove biofilms. The synthesis reaction parameters of iron oxide nanoparticles was also assessed using statistical modeling to allow for large scale synthesis of magnetic nanoparticles. The third section of this dissertation focuses on the synergism of magnetic nanoparticles and magnetic fields with current antimicrobials through the use of FDA approved inactive ingredients. Potential formulations were evaluated using an accelerated stability and efficacy study, while prototype magnetic field devices for treating oral caries biofilms were also developed. In sum, this work represents key steps towards slowing the rise in antibiotic resistance while ensuring treatment of chronic biofilm infections by using magnetic-based mitigation of biofilms

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