COM BATI NG I N F ECTION

Nanoscale silver for infection control By Bridgette C. Williams, MSN, RN, MAMS

NANOSCIENCE IS THE STUDY of extremely small objects, and nanotechnology is technology that’s conducted at the nanoscale, which is about 1 to 100 nanometers (nm).1 One nanometer is one billionth of a meter.1,2 Nanomedicine is a division of nanotechnology defined as highly specific medical interventions at the molecular scale for curing disease or repairing damaged tissues.3 To date, more than 245 nanosize developments specific to nanomedicine have been developed. This article focuses on one of these developments: the use of nanoscale silver to kill bacteria and viruses.4 Silver as an antimicrobial Besides its highly conductive properties as a metal, silver (Ag) is a natural biocide, meaning it can kill microbes.5,6 Documented use of silver as an antimicrobial to prevent spoilage of water or wine stored in vessels dates back thousands of years before microorganisms were viewable by microscope.7 Four different forms of oxidized silver (Ag0, Ag+, Ag2+, Ag3+) kill many microbes; Ag0 and Ag+ are the most common.8-10 The exact mechanism by which oxidized silver kills microbes isn’t completely understood, but it’s been shown to eliminate more than 650 different types of microbes and is used to purify water.12 Silver nitrate (AgNO3) is a compound derived from silver. It’s topically applied to treat ulcers and warts.5,11,13,14 In humans, silver concentrates in the skin, liver, spleen, and adrenal glands.15 If inhaled, silver irritates the airways and lungs, leading to breathing problems.15 In blood, silver is detectable at low levels, normally less than 5 mcg/dL.6,16 Prolonged contact with or use of silver is associated with

argyria, which results in gray to grayblack staining of the skin and mucous membranes. It usually doesn’t cause any serious adverse health effects.16 Both silver and nanoscale silver release oxidized ions (Ag+), which disrupt and kill microbes.17 However, nanoscale silver particles are different when compared with the relatively larger bulk form. The nanoscale silver particles’ large surface-to-volume ratio means they cover more of a structure’s surface area and react faster than silver in the larger form.9 The smaller the nanoscale silver particle, the greater its effect as an antimicrobial.9,18 The size and shape of particles differ, which affects the amount and release rate of Ag+ and the level of concentration in the organs.19,20 In addition, nanoscale silver releases Ag+ continuously for a specified time.19 Nanoscale silver is currently used in more consumer products than any other nanomaterial.18 Nanoscale silver has been manufactured and marketed in clothing, food containers, kitchen utensils, sprays, baby wipes, toys, laundry detergents, wall paint, washing machines, cosmetics, soaps, cleansers, toothbrushes, toothpaste, and fabric softeners for its antibacterial properties.9,10,18,19,21-23 Healthcare uses The increase in antibiotic-resistant microbes has promoted interest in developing nanoscale silver for use in healthcare and medical research.17 Coating the surface of certain medical devices with nanoscale silver can help prevent biofilm, which is unrestricted bacterial growth on a surface; the layer of growth inhibits the effect of antimicrobials.9,10,24 Nanoscale silver is effective at eliminating fungi,

viruses, and Gram-negative and Gram–positive bacteria.4,9,12,13 Wound dressings that incorporate nanoscale silver into the layers of the dressing are often used to reduce bacterial load.17 Microbial resistance to nanoscale silver is rare, but, it can occur under special circumstances.12,14,19,25,26 Nanoscale silver decreases wound healing time and scarring as it decreases bacterial load and inflammation in infected wounds.4 Some intrathecal catheters are coated with nanoscale silver particles.6,26 Unintended effects Nanoscale silver toxicity has been described in vivo and in vitro studies.10,27-29 Cumulative exposure to silver ions is possible due to the multiple applications in consumer products, medical products, and purification of water in the environment.13,28 Exactly how nanoscale silver can cause toxicity isn’t understood but, due to its variation in extremely small sizes, nanoscale silver can accumulate in organs and tissues such as the liver and spleen, leading to adverse cellular changes.10,27,28 The likelihood of nanosilver toxicity is linked to repeated exposure. The liver, lungs, and spleen are most likely to retain nanosized particles as the body eliminates the nanoscale silver.20,28 Keeping it safe Follow the manufacturer’s instructions for use to provide optimal patient care using nanoscale silverbased medications or medical devices. Be sure to: • use personal protective equipment (PPE) as directed by facility policy. • monitor the patient’s serum Ag levels as prescribed.

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• obtain and monitor the results of 24-hour urine specimens for Ag as prescribed. • assess for pulmonary, hepatic, and renal dysfunction.28,30 The risks and benefits of nanoscale silver-based medications and medical devices are mostly limited to findings from animal studies.18,26,28,31,32 Nurses can contribute to the knowledge base by documenting assessment data in patients receiving nanoscale silver-based medications. ■ REFERENCES 1. National Nanotechnology Initiative. What is nanotechnology? http://www.nano.gov/. 2. Meetoo D. Nanotechnology: science fiction or a future reality? Br J Nurs. 2011;20(12):713. 3. Sheng WY, Huang L. Cancer immunotherapy and nanomedicine. Pharm Res. 2011;28(2):200-214. 4. Etheridge ML, Campbell SA, Erdman AG, Haynes CL, Wolf SM, McCullough J. The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine. 2013;9(1):1-14. 5. Guarneri PFM. A systematic review of silverreleasing dressings in the treatment of burns. Capsula Eburnea. 2011;6:15-19. 6. Wong KKY, Liu X. Silver nanoparticles—the real “silver bullet” in clinical medicine? Med Chem Comm. 2010;1(2):125-131. 7. Alexander JW. History of the medicinal use of silver. Surg Infect. 2009;10(3):289-292. 8. Galdiero S, Falanga A, Vitiello M, Cantisani M, Marra V, Galdiero M. Silver nanoparticles as potential antiviral agents. Molecules. 2011;16(10):8894-8918. 9. Wijnhoven SWP, Peijnenburg WJGM, Herberts CA, et al. Nano-silver: a review of available data and knowledge gaps in human and environmental risk assessment. Nanotoxicology. 2009;3(2):109-138. 10. U.S. Environmental Protection Agency. State of the science literature review: everything nanosilver and more. Washington, DC; 2010. 11. Chaloupka K, Malam Y, Seifalian AM. Nanosilver as a new generation of nanoproduct in biomedical applications. Trends Biotechnol. 2010;28(11):580-588. 12. Gunawan C, Teoh WY, Marquis CP, Amal R. Induced adaptation of bacillus sp. to antimicrobial nanosilver. Small. 2013;9(21):3554-3560. 13. Lee J, Kim K-J, Sung WS, Kim JG, Lee DG. The silver nanoparticle (nano-Ag): a new model for antifungal agents. In: Perez DP, ed. Silver Nanoparticles. Rijeka, Croatia: INTECH; 2010:295-308. 14. Ayala-Nunez NV, Lara Villegas HH, Del Carmen Ixtepan Turrent L, Rodriguez Padilla C. Silver nanoparticles toxicity and bactericidal effect agains methicillin-resistant Staphycococcus aureus: nanoscale does matter. Nanobiotechnology. 2009;5(1-4):2-9. 15. Kubba A, Kubba R, Batrani M, Pal T. Argyria an unrecognized cause of cutaneous pigmentation in Indian patients: a case series and review of the literature. Indian J Dermatol Venereol Leprol. 2013;79(6):805-811. www.Nursing2014.com

16. Padlewska KK. Argyria. 2013. http://emedicine. medscape.com/article/1069121-overview. 17. Rai M, Yadav A, Gade A. Silver nanoparticles as a new generation of antimicrobials. Biotechnol Adv. 2009;27(1):76-83. 18. Luoma SN. Silver Nanotechnologies and the Environment: Old Problem or New Challenges? Project on Emerging Technology. Washington DC: The Pew Charitable Trusts; 2008. 19. Lara H, Ayala-Nunez N, Ixtepan Turrent L, Rodriguez Padilla C. Bactericidal effect of silver nanoparticles against multidrug-resistant bacteria. World J Microbiol Biotechnol. 2010;26(4):615-621. 20. Lankveld DP, Oomen AG, Krystek P, et al. The kinetics of the tissue distribution of silver nanoparticles of different sizes. Biomaterials. 2010;31(32):8350-8361. 21. Chen X, Schluesener HJ. Nanosilver: a nanoproduct in medical application. Toxicol Lett. 2008;176(1):1-12. 22. Marambio-Jones C, Hoek EM. A review of the antibacterial effects of silver nanomaterials and potential implications for human health and the environment. J Nanoparticle Res. 2010;12(5):1531-1551. 23. Roychuk E. Silver nanoparticle use spurs U.S. consumer databsase. 2013. http://www.cbc.ca/ news/technology/silver-nanoparticle-use-spurs-us-consumer-database-1.2415424. 24. Simchi A, Tamjid E, Pishbin F, Boccaccini AR. Recent progress in inorganic and composite coatings with bactericidal capability for orthopaedic applications. Nanomedicine. 2011;7(1):22-39. 25. Annear DI, Mee BJ, Bailey M. Instability and linkage of silver resistance, lactose fermentation, and colony structure in Enterobacter cloacae from burn wounds. J Clin Pathol. 1976;29(5):441-443. 26. Brandt O, Mildner M, Egger AE, et al. Nanoscalic silver possesses broad-spectrum antimicrobial activities and exhibits fewer toxicological side effects than silver sulfadiazine. Nanomedicine. 2012;8(4):478-488. 27. Yildirimer L, Thanh NT, Loizidou M, Seifalian AM. Toxicology and clinical potential of nanoparticles. Nano Today. 2011;6(6):585-607. 28. Ahamed M, Alsalhi MS, Siddiqui MK. Silver nanoparticle applications and human health. Clin Chim Acta. 2010;411(23-24):1841-1848. 29. Munger MA, Radwanski P, Hadlock GC, et al. In vivo human time-exposure study of orally dosed commercial silver nanoparticles. Nanomedicine. 2014;10(1):1-9. 30. Heinemann M, Schäfer HG. Guidance for handling and use of nanomaterials at the workplace. Hum Exp Toxicol. 2009;28(6-7):407-411. 31. Samberg ME, Oldenburg SJ, Monteiro-Riviere NA. Evaluation of silver nanoparticle toxicity in skin in vivo and keratinocytes in vitro. Environ Health Perspect. 2010;118(3):407-413. 32. Hendi A. Silver nanoparicles mediate differential responses in some of liver and kidney functions during skin wound healing. J King Saud Univ Sci. 2011;23(1):47-52. Bridgette C. Williams is a new graduate nurse educator at the State University of New York Institute of Technology in Utica, N.Y. The author has disclosed that she has no financial relationships related to this article. DOI-10.1097/01.NURSE.0000444550.50617.1d

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Nanoscale silver for infection control.

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