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LITERATURE REVIEW IN THE USE OF NANOPARTICLE FORMULATIONS OF SILVER (AG), GOLD (AU), AND

LITERATURE REVIEW IN THE USE OF NANOPARTICLE FORMULATIONS OF SILVER (AG), GOLD (AU), AND ZINC (ZN) AS ANTI-INFECTIVE AGENTS. William Evans, Austin Sack and Sherlie Llorens. Preceptor: Dr. Ashley Spies. November 2, 2018. INTRODUCTION.  Objective.

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LITERATURE REVIEW IN THE USE OF NANOPARTICLE FORMULATIONS OF SILVER (AG), GOLD (AU), AND

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  1. LITERATURE REVIEW IN THE USE OF NANOPARTICLE FORMULATIONS OF SILVER (AG), GOLD (AU), AND ZINC (ZN) AS ANTI-INFECTIVE AGENTS William Evans, Austin Sack and Sherlie Llorens Preceptor: Dr. Ashley Spies November 2, 2018

  2. INTRODUCTION  Objective  Conduct a literature review of metal nanoparticles and their use as an alternative to antimicrobial agents  Why?  Pathogen resistance to antimicrobials has become increasingly problematic  Significant gaps in knowledge within this field  Nanotechnology within the field of antimicrobial agents  Benefits: Decreased toxicity and cost, while overcoming resistance  Goal  Understand the bioactivities of metal nanoparticles in order to understand past research and gaps in knowledge within this field Image retrieved from: https://www.med.uottawa.ca/sim/data/Images/Antibiotic_resistance_cartoon.jpg

  3. METHODS AND RESULTS OVERVIEW Methods  PubMed Search  Silver:  Mesh Terms: Metal, Anti-Infective Agents, Nanoparticles 112 Total Articles  Filters: Review article, past 5 years  Gold  Mesh Terms: Metal, Anti-Infective Agents, Nanoparticles  Filters: Review article, past 5 years  Zinc 37  Mesh Terms: Metal, Anti-Infective Agents, Nanoparticles Relevant Articles  Filters: Past 5 years* Results  112 Articles found in our search of silver, gold and zinc  37 of these were relevant to the bioactivities of interest (e.g. mechanism of action, toxicity, and application) Figure 1: Total articles evaluated in the study

  4. RESULTS- SILVER Table 1: Results obtained Silver nanoparticles (12/52 articles)

  5. RESULTS- GOLD Table 2: Results obtained Gold nanoparticles ​(11/20 articles)

  6. RESULTS-ZINC Table 3: Results obtained Zinc nanoparticles ​(14/40 articles)

  7. SILVER: MECHANISM OF ACTION  2 proposed mechanisms  Contact killing  Ion-dependent manner Figure 2 : Qing Y, Cheng L, Li R, et al. Potential antibacterial mechanism of silver nanoparticles and the optimization of orthopedic implants by advanced modification technologies. Int J Nanomedicine. 2018;13:3311-3327.

  8. SILVER: TOXICITY • High concentrations of silver nanoparticles are toxic and can cause various health problems • Argyria – skin toxicity • Argyrosis – eye toxicity Figure 3: Argyrosis Figure 4: Argyria Figures 3 & 4: retrieved from: https://jamanetwork.com/data/Journals/DERM/926965/dlv130005f1.png http://2.bp.blogspot.com/-Sm24tr3u3L4/Twv99m8DHeI/AAAAAAAAB7E/P-K5ygWx6wE/s1600/Argyrosis+-+Silver+Poisoning+%25282%2529.jpg

  9. SILVER: APPLICATIONS  Antibacterial activity against  E. coli  S. aureus  S. mutans  S. epidermis  Medical  Wound/burn healing  Artificial joint replacements  Surgery infection prophylaxis  Cleaning chemicals  Fabric cleaners Figure 5: Image retrieved from: https://sep.yimg.com/ay/yhst- 128880362216497/acticoat-flex-3-7-silver-dressings-by-smith-nephew-2.jpg  Solar energy collectors

  10. MECHANISM OF ACTION: GOLD  Change in membrane potential and prevention of ATPase activities  Inhibition of ribosome subunit binding for tRNA Figure 6: Vimbela, G. V, & Fraze, C. (2017). Antibacterial properties and toxicity from metallic nanomaterials.

  11. GOLD: TOXICITY  Production of ROS  Irreversible blocking of potassium ion channels  Cytotoxic effects seen when nanoparticles are <2nm Figure 7 & 8 : Schmid, G., Kreyling, W. G., & Simon, U. (2017). Toxic effects and biodistribution of ultrasmall gold nanoparticles. Archives of Toxicology, 91(9), 3011– 3037.

  12. GOLD: APPLICATIONS  Antibacterial activity against  Pseudomonas aeruginosa  Salmonella typhi  E. Coli  S. Aureus  S. Epidermidis  Cancer treatment Figure 9: Mocan, L., Pop, T., Mosteanu, O., Agoston-coldea, L., Matea, C. T., Gonciar, D., & Zdrehus, C. (2017). Laser thermal ablation of multidrug-resistant bacteria using functionalized gold nanoparticles, 2255–2263.  Thermal ablation therapy

  13. MECHANISM OF ACTION: ZINC  Antimicrobial activity  unknown  Proposed mechanisms:  Production of Zn ions and radical oxygen species (ROS)27,34  Release of Zn2+ ions as a result of ZnO decomposition27,34  The electrostatic interaction between ZnO NPs and bacteria cell surface, prompted damage and subsequent membrane breakdown27,34 Figure 10: ZnO proposed mechanism of action retrieved from https://www.sciencedirect.com/science/article/pii/S2468203917300560#fig2

  14. ZINC: TOXICITY  Toxic levels27  Not well established  Due to the low doses used for efficacy  High systemic concentration of zinc can lead to:  Nausea and Vomiting  Stomach pain  Diarrhea Figure 11: Retrieved from https://www.ganjllc.com/impact-ethnicity-digestive-diseases/

  15. ZINC: APPLICATIONS  Bactericidal  Gram positive, Gram negative and antifungal coverage:  Escherichia coli  Staphylococcus aureus  Staphylococcus epidermidis  Drug forms and formulations:  Hydrogels7 Figure 12: Hydrogel  Prosthetic coating  Wound dressings5 Figure 13: Wound dressings Figures 13 and 14 Retrieved from https://parthenoninc.com/dermagran-amorphous-zinc-saline-hydrogel-dressing-3-oz/ . https://www.google.com/search?hl=en&q=hydrogel+dressing&tbm=isch&tbs=simg:CAQSlgEJLVWfEyjbm3Iai

  16. CONCLUSION  Metal nanoparticles are a promising alternative to commonly used anti- microbials  Gaps in knowledge exist which must be understood before the area can be advanced  This project has allowed us to use information gathered from several different studies in the past 5 years and to develop a summary in the form an information table

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  18. REFERENCES CONT. 17. Kumar, R., Agarwal, M., & Balani, K. (2016). Effect of ZnO morphology on affecting bactericidal property of ultra high molecular weight polyethylene biocomposite, 62, 843–851. https://doi.org/10.1016/j.msec.2016.02.032 18. Maleki, S., Lot, F., Barzegar-jalali, M., & Ag, O. (2014). Antimicrobial activity of the metals and metal oxide nanoparticles, 44, 278–284. https://doi.org/10.1016/j.msec.2014.08.031 19. Mocan, L., Pop, T., Mosteanu, O., Agoston-coldea, L., Matea, C. T., Gonciar, D., & Zdrehus, C. (2017). Laser thermal ablation of multidrug-resistant bacteria using functionalized gold nanoparticles, 2255– 2263. 20. Mocan, T., Matea, C. T., Pop, T., Mosteanu, O., Buzoianu, A. D., Puia, C., … Mocan, L. (2017). Development of nanoparticle - based optical sensors for pathogenic bacterial detection. Journal of Nanobiotechnology, 1–14. https://doi.org/10.1186/s12951-017-0260-y 21. Patil, M. P., & Kim, G. (2017). Eco-friendly approach for nanoparticles synthesis and mechanism behind antibacterial activity of silver and anticancer activity of gold nanoparticles. Applied Microbiology and Biotechnology, 79–92. https://doi.org/10.1007/s00253-016-8012-8 22. Rajeshkumar, S., & Bharath, L. V. (2017). Chemico-Biological Interactions Mechanism of plant-mediated synthesis of silver nanoparticles e A review on biomolecules involved , characterisation and antibacterial activity. Chemico-Biological Interactions, 273, 219–227. https://doi.org/10.1016/j.cbi.2017.06.019 23. Schmid, G., Kreyling, W. G., & Simon, U. (2017). Toxic effects and biodistribution of ultrasmall gold nanoparticles. Archives of Toxicology, 91(9), 3011–3037. https://doi.org/10.1007/s00204-017-2016-8 24. Shah, M., Badwaik, V., Kherde, Y., Waghwani, H. K., Modi, T., & Aguilar, Z. P. (2014). Gold nanoparticles: various methods of synthesis and antibacterial applications Monic, (8), 1320–1344. 25. Shedbalkar, U., Singh, R., Wadhwani, S., Gaidhani, S., & Chopade, B. A. (2014). Microbial synthesis of gold nanoparticles : Current status and future prospects. Advances in Colloid and Interface Science, 209, 40–48. https://doi.org/10.1016/j.cis.2013.12.011 26. Siddiqi, K. S., Husen, A., & Rao, R. A. K. (2018). A review on biosynthesis of silver nanoparticles and their biocidal properties. Journal of Nanobiotechnology. https://doi.org/10.1186/s12951-018-0334-5 27. Vimbela, G. V, & Fraze, C. (2017). Antibacterial properties and toxicity from metallic nanomaterials. 28. Wahid, F., Zhou, Y., Wang, H., Wan, T., Zhong, C., & Chu, L. (2018). International Journal of Biological Macromolecules Injectable self-healing carboxymethyl chitosan-zinc supramolecular hydrogels and their antibacterial activity. International Journal of Biological Macromolecules, 114, 1233–1239. https://doi.org/10.1016/j.ijbiomac.2018.04.025 29. Wesam Salem, Deborah R. Leitner, Franz G. Zingl, Gebhart Schratter, Ruth Prassl, W. G., & Joachim Reidl, and S. S. (2015). Antibacterial activity of silver and zinc nanoparticles against Vibrio cholerae and enterotoxic Escherichia coli, 305(1), 85–95. 30. Xu, C., Cai, Y., Ren, C., Gao, J., & Hao, J. (2015). Zinc-Triggered Hydrogelation of, 1–7. https://doi.org/10.1038/srep07753 31. Zhang, H., Jung, J., & Zhao, Y. (2016). Preparation , characterization and evaluation of antibacterial activity of catechins and catechins – Zn complex loaded ␤ -chitosan nanoparticles of different particle sizes. Carbohydrate Polymers, 137, 82–91. https://doi.org/10.1016/j.carbpol.2015.10.036 32. Zhang, X., Liu, Z., Shen, W., & Gurunathan, S. (2016). Silver Nanoparticles : Synthesis , Characterization , Properties , Applications , and Therapeutic Approaches. https://doi.org/10.3390/ijms17091534 33. Yamada, M., Foote, M., & Prow, T. W. (2015). Therapeutic gold, silver, and platinum nanoparticles, 7(June). https://doi.org/10.1002/wnan.1322 34. Zhang, L., Jiang, Y., Wen, D., Ding, Y., (2016). Role of physical and chemical interactions in the antibacterial behavior of ZnO nanoparticles against E. coli. https://doi:10.1016/j.msec.2016.08.044.

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