Author: Melanie Fuller
Fuller, Melanie, 2020 The gold standard; enhancing antibiotic effectiveness through gold nanoparticles, Flinders University, College of Science and Engineering
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Antibiotic resistance is predicted to become one of the greatest threats to humanity and we need to start acting now to find alternative treatment methods. As a short-term solution, this research has explored the use of gold nanoparticles to enhance antibiotic effectiveness whilst also lowering the dosage of the antibiotic.
Gold nanoparticles were chosen as the main component in this work due to their biocompatibility as well as their favourable optical and physical properties. In this thesis, the polyelectrolyte coating parameters of gold nanoparticles were optimised to ensure stability of the nanoparticles, which is vital in medical applications. The stabilised nanoparticles were then used to pre-treat Gram-negative membrane models before addition of the membrane active antibiotic, Colistin. Pre-treatment with nanoparticles prior to the addition of Colistin showed increased defect formation after the Colistin was removed compared to using Colistin alone. It was also found that high concentrations of gold nanoparticles caused defects on the membrane's surface, likely through binding to the outer membrane.
In addition to the pre-treatment, the use of Colistin coated gold nanoparticles were evaluated to reduce the amount of Colistin required to kill bacteria. It was found that the gold nanoparticles were more stable when coated with Colistin and cationic polyelectrolyte, compared to coating with Colistin only. The anionic Colistin coated nanoparticles had a 6.8-fold decrease in the amount of Colistin required to achieve the minimum inhibitory concentration, compared to Colistin alone. This study also determined that the addition of either cationic or anionic gold nanoparticles to bacteria do not inhibit bacterial growth, indicating they are not inherently antimicrobial.
Following the successes of utilising polyelectrolyte coated gold nanoparticles in antibiotic treatment, a wound dressing application was considered and a proof-of-concept antibiotic loaded bandage was produced. The nanomesh bandage was fabricated through electrospinning, incorporating Colistin into the mesh. The drug release profile could be modified through addition of gold nanoparticles during mesh formation. Although this research is only in its infancy, it has shown promising results, with the addition of anionic gold nanoparticles into the mesh leading to sufficient release of Colistin over 14 days to kill E. coli.
In summary, this thesis explores a wide range of disciplines and brings together new knowledge of increasing susceptibility to Colistin with the use of gold nanoparticles. Although the problem of antibiotic resistance is significant, this work will further the knowledge base to help us move toward an eventual solution.
Keywords: Nanoparticles, nanomesh, gold, antibiotics
Subject: Chemistry thesis
Thesis type: Doctor of Philosophy
Completed: 2020
School: College of Science and Engineering
Supervisor: Ingo Koeper