Original Scientific Article
Effect of silver nanoparticles on healing of third-degree burns infected with Pseudomonas aeruginosa in laboratory mice
Mukhallad Abdul Kareem Ramadhan*,
Abbas Najee Balasm,
Sanaa Basher Kadhm,
Haider Faleh Al-Saedi

Mac Vet Rev 2021; 44 (1): i - xii


Received: 16 February 2020

Received in revised form: 24 October 2020

Accepted: 06 November 2020

Available Online First: 11 December 2020

Published on: 15 March 2021

Correspondence: Mukhallad Abdul Kareem Ramadhan, mukalad.mcm@uomisan.edu.iq


The treatment of full-thickness skin burn using nanomaterials is promising as a medical application reducing the risk of infection and severe dermal scarring. Therefore, this study aims to evaluate the effectiveness of nanomaterials, particularly 3% silver nanoparticles containing ointment (3% SNO), on the full-thickness skin burn of laboratory mice. A total number of 36 male mice were used, equally divided into three groups: negative control (not burned and not treated); positive control (+ve) (burned and treated with castor oil and white petroleum jelly); and SNO-treated group (burned and treated with 3% SNO). The skin of the animals’ back was shaved. A 2x0.5 cm metal plate was heated on a burner to burn the skin of the animals of positive control and SNO-treated groups. Pseudomonas aeruginosa bacterial suspension was applied to the burnt area. The application of SNO, as well as the mixture of white petroleum jelly and castor oil, was started after 6 hours of inducing burns and continued for 14 days (three times daily) in the respected groups. The SNO-treated group showed accelerated healing within 14 days demonstrated by re-epithelialization of the epidermal layer and proliferation of the fibroblasts in the dermal layer. Less healing evidence was observed in the +ve control group in the same period. In conclusion, to our knowledge, this is the first study that uses a 3% SNO formula and has found that it has a promising impact on the treatment of infected skin burns.

Keywords: silver nanoparticles, skin burns, silver ointment, skin healing, infected burns


  1. Zhou, E.H., Watson, C., Pizzo, R., Cohen, J., Dang, Q., Ferreira de Barros, P.M., Park, C.Y., et al. (2014). Assessing the impact of engineered nanoparticles on wound healing using a novel in vitro bioassay. Nanomedicine (Lond.). 9(18): 2803-2815. https://doi.org/10.2217/nnm.14.40 PMid:24823434 PMCid:PMC4684260
  2. McLaughlin, S., Podrebarac, J., Ruel, M., Suuronen, E.J., McNeill, B., Alarcon, E.I. (2016). Nano-engineered biomaterials for tissue regeneration: what has been achieved so far? Front. Mater. 3, 27. https://doi.org/10.3389/fmats.2016.00027
  3. Jain, J., Arora, S., Rajwade, J.M., Omray, P., Khandelwal, S., Paknikar, K.M. (2009). Silver nanoparticles in therapeutics: development of an antimicrobial gel formulation for topical use. Mol Pharm. 6(5): 1388-1401. https://doi.org/10.1021/mp900056g PMid:19473014           
  4. Rigo, C., Ferroni, L., Tocco, I., Roman, M., Munivrana, I., Gardin, C., Cairns, W.R., et al. (2013). Active silver nanoparticles for wound healing. Int J Mol Sci. 14(3): 4817-4840. https://doi.org/10.3390/ijms14034817 PMid:23455461 PMCid:PMC3634485       
  5. Klasen, H.J. (2000). A historical review of the use of silver in the treatment of burns. II. Renewed interest for silver. Burns 26(2): 131-138. https://doi.org/10.1016/S0305-4179(99)00116-3
  6. Klasen, H.J. (2000). Historical review of the use of silver in the treatment of burns. I. Early uses. Burns 26(2): 117-130. https://doi.org/10.1016/S0305-4179(99)00108-4
  7. Hussain, S., Ferguson, C. (2006). Best evidence topic report. Silver sulphadiazine cream in burns. Emerg Med J. 23(12): 929-932. https://doi.org/10.1136/emj.2006.043059 PMid:17130603 PMCid:PMC2564257
  8. Okan, D., Woo, K., Sibbald, R.G. (2007). So what if you are blue? Oral colloidal silver and argyria are out: safe dressings are in. Adv Skin Wound Care. 20(6): 326-330. https://doi.org/10.1097/01.ASW.0000276415.91750.0f PMid:17538258 
  9. Cutting, K., White, R., Edmonds, M. (2007). The safety and efficacy of dressings with silver - addressing clinical concerns. Int Wound J. 4(2): 177-184. https://doi.org/10.1111/j.1742-481X.2007.00338.x PMid:17651232         
  10. Fong, J., Wood, F. (2006). Nanocrystalline silver dressings in wound management: a review. Int J Nanomedicine. 1(4): 441-449. https://doi.org/10.2147/nano.2006.1.4.441 PMid:17722278 PMCid:PMC2676636
  11. Burd, A., Kwok, C.H., Hung, S.C., Chan, H.S., Gu, H., Lam, W.K., Huang, L. (2007). A comparative study of the cytotoxicity of silver-based dressings in monolayer cells, tissue explants, and animal models. Wound Repair Regen. 15(1): 94-104. https://doi.org/10.1111/j.1524-475X.2006.00190.x PMid:17244325
  12. Tegos G.P., Demidova T.N., Arcila-Lopez D., Lee H., Wharton T., Gali H., Hamblin, M.R. (2005). Cationic fullerenes are effective and selective antimicrobial photosensitizers. Chem Biol. 12(10): 1127-1135. https://doi.org/10.1016/j.chembiol.2005.08.014 PMid:16242655 PMCid:PMC3071678
  13. Robins, E.V. (1990). Burn shock. Crit Care Nurs Clin North Am. 2(2): 299-307. https://doi.org/10.1016/S0899-5885(18)30830-X
  14. Dai, T., Huang, Y.Y., Sharma, S.K., Hashmi, J.T., Kurup, D.B., Hamblin, M.R. (2010). Topical antimicrobials for burn wound infections. Recent Pat Antiinfect Drug Discov. 5(2): 124-151. https://doi.org/10.2174/157489110791233522 PMid:20429870 PMCid:PMC2935806       
  15. Hendi, A. (2011). Silver nanoparticles mediate differential responses in some of liver and kidney functions during skin wound healing. J King Saud Uni. 23(1): 47-52. https://doi.org/10.1016/j.jksus.2010.06.006
  16. Cordeiro, M.F. (2002). Beyond mitomycin: TGF-beta and wound healing. Prog Retin Eye Res. 21(1): 75-89. https://doi.org/10.1016/S1350-9462(01)00021-0
  17. Adhya, A., Bain, J., Ray, O., Hazra, A., Adhikari, S., Dutta, G., Ray, S., Majumdar, B.K. (2014). Healing of burn wounds by topical treatment: A randomized controlled comparison between silver sulfadiazine and nano-crystalline silver. J Basic Clin Pharm. 6(1): 29-34. https://doi.org/10.4103/0976-0105.145776 PMid:25538469 PMCid:PMC4268627
  18. Tian, J., Wong, K.K., Ho, C.M., Lok, C.N., Yu, W.Y., Che, C.M., Chiu, J.F., Tam, P.K. (2007). Topical delivery of silver nanoparticles promotes wound healing. Chem Med Chem. 2(1): 129-136. https://doi.org/10.1002/cmdc.200600171 PMid:17075952           
  19. Sibbald, R.G., Contreras-Ruiz, J., Coutts, P., Fierheller, M., Rothman, A., Woo, K. (2007). Bacteriology, inflammation, and healing: a study of nanocrystalline silver dressings in chronic venous leg ulcers. Adv Skin Wound Care. 20(10): 549-558. https://doi.org/10.1097/01.ASW.0000294757.05049.85 PMid:17906429
  20. Nadworny, P.L., Wang, J., Tredget, E.E., Burrell, R.E. (2008). Anti-inflammatory activity of nanocrystalline silver in a porcine contact dermatitis model. Nanomedicine. 4(3): 241-251. https://doi.org/10.1016/j.nano.2008.04.006 PMid:18550449       
  21. Wright, J.B., Lam, K., Buret, A.G., Olson, M.E., Burrell, R.E. (2002). Early healing events in a porcine model of contaminated wounds: effects of nanocrystalline silver on matrix metalloproteinases, cell apoptosis and healing. Wound Rep Regen. 10, 141-151. https://doi.org/10.1046/j.1524-475X.2002.10308.x PMid:12100375         
  22. Huang, Y., Li, X., Liao, Z., Zhang, G., Liu, Q., Tang, J., Peng, Y., Liu, X., Luo, Q. (2007). A randomized comparative trial between Acticoat and SD-Ag in the treatment of residual burn wounds, including safety analysis. Burns 33(2): 161-166. https://doi.org/10.1016/j.burns.2006.06.020 PMid:17175106
  23. Saha, A., Kumar Giri, N., Agarwal, S.P. (2017). Silver nanoparticle-based hydrogels of tulsi extracts for topical drug delivery. Int J Ayurveda Pharma Res. 5(1): 17-23.
  24. Dandasi, J.D., Jayaprakash, J.S., Kulkarni, P.K., Akhila, A.R., Namratha, S.S. (2020). Formulation and evaluation of different topical dosage forms for wound healing properties. Int J Pharm Sci Res. 1, 10-23.
  25. Patel, J., Patel, B., Banwait, H., Parmar, K., Patel, M. (2011). Formulation and evaluation of topical Aceclofenac gel using different gelling agents. Int J Drug Dev & Res. 3(1): 156-164.
  26. Mayr-Harting, A., Hedges, A., Berkeley, R. (1972). Methods for studying bactericides. In: Norris, J. R., D. W. Ribbons (Eds.), Methods in Microbiology. Vol. 7A (p. 74). New York: Academic Press. https://doi.org/10.1016/S0580-9517(08)70618-4
  27. Tymen, S.D., Rojas, I.G, Zhou, X., Fang, Z.J., Zhao, Y., Marucha, P.T. (2013). Restraint stress alters neutrophil and macrophage phenotypes during wound healing. Brain Behav Immun. 28, 207-217. https://doi.org/10.1016/j.bbi.2012.07.013 PMid:22884902 PMCid:PMC3878450
  28. Crichton, M.L., Chen, X., Huang, H., Kendall, M.A. (2013). Elastic modulus and viscoelastic properties of full-thickness skin characterized at micro scales. Biomaterials 34(8): 2087-2097. https://doi.org/10.1016/j.biomaterials.2012.11.035 PMid:23261214        
  29. Reed, L.J., Muench, H. (1938). A simple method of estimating fifty percent endpoints. Am J Hyg. 27(3): 493-497. https://doi.org/10.1093/oxfordjournals.aje.a118408
  30. Adedapo, A., Babarinsa, O., Oyagbemi, A., Adedapo, A., Omobowale, T. (2016). Cardiotoxicity study of the aqueous extract of corn silk in rats. Mac Vet Rev. 39 (1): 43-49. https://doi.org/10.1515/macvetrev-2015-0065
  31. Rance, R.W. (1973). Studies of the factors controlling the action of hair sprays-I: the spreading of hair spray resin solutions on hair. J Soc Cosmet Chem. 24, 501-522.
  32. Jones, D.S., Woolfson A.D., Brown A.F. (1997). Texture analysis and flow rheometry of novel, bioadhesive antimicrobial oral gels. Pharm Res. 14(4): 450-457. https://doi.org/10.1023/A:1012091231023 PMid:9144730           
  33. Slistan-Grijalva, A., Herrera-Urbina, R., Rivas-Silva, J.F., Avalos-Borja, M., Castillon-Barraza, F.F., Posada-Amarillas, A. (2005). Classical theoretical characterization of the surface plasmon absorption band for silver spherical nanoparticles suspended in water and ethylene glycol. Physica E. 27, 104-112. https://doi.org/10.1016/j.physe.2004.10.014
  34. Shrivastava, S., Bera, T., Roy, A., Singh, G., Ramachandrarao, P., Dash, D. (2007). Characterization of enhanced antibacterial effects of novel silver nanoparticles. Nanotechnology 18, 103-112. https://doi.org/10.1088/0957-4484/18/22/225103
  35. Litvin, V.A., Minaev, B.F. (2013). Spectroscopy study of silver nanoparticles fabrication using synthetic humic substances and their antimicrobial activity. Spectrochim Acta A Mol Biomol Spectrosc. 108, 115-122. https://doi.org/10.1016/j.saa.2013.01.049 PMid:23466321        
  36. Heydarnejad, M.S., Rahnama, S., Mobini-Dehkordi, M., Yarmohammadi, P., Aslnai, H. (2014). Silver nanoparticles accelerate skin wound healing in mice (Mus musculus) through suppression of the innate immune system. Nanomed J. 1(2): 79-87.  
  37. You, C., Li, Q., Wang, X., Wu, P., Ho, J.K., Jin, R., Zhang, L., Shao, H., Han, C. (2017). Silver nanoparticle loaded collagen/chitosan scaffolds promote wound healing via regulating fibroblast migration and macrophage activation. Sci Rep. 7(1): 1-11. https://doi.org/10.1038/s41598-017-10481-0 PMid:28874692 PMCid:PMC5585259
  38. Chanan-Khan, A., Szebeni, J., Savay, S., Liebes, L., Rafique, N.M., Alving, C.R., Muggia F,M. (2003). Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil): possible role in hypersensitivity reactions. Ann Oncol. 14(9): 1430-1437. https://doi.org/10.1093/annonc/mdg374 PMid:12954584            
  39. Zhang, S., Liu, X., Wang, H., Peng, J., Wong, K.K. (2014). Silver nanoparticle-coated suture effectively reduces inflammation and improves mechanical strength at intestinal anastomosis in mice. J Pediatr Surg. 49(4): 606-613. https://doi.org/10.1016/j.jpedsurg.2013.12.012 PMid:24726122 
  40. Gohel, M.S., Windhaber, R.A., Tarton, J.F., Whyman, M.R., Poskitt, K.R. (2008). The relationship between cytokine concentrations and wound healing in chronic venous ulceration. J Vasc Surg. 48(5): 1272-1277. https://doi.org/10.1016/j.jvs.2008.06.042 PMid:18771884       
  41. Franková, J., Pivodová, V., Vágnerová, H., Juráňová, J., Ulrichová, J. (2016). Effects of silver nanoparticles on primary cell cultures of fibroblasts and keratinocytes in a wound-healing model. J Appl Biomater Funct Mater. 14(2): e137-142. https://doi.org/10.5301/jabfm.5000268 PMid:26952588 


© 2020 Ramadhan M.A.K. This is an open-access article published under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Conflict of Interest Statement

The authors have declared that no competing interests exist.

Citation Information

Macedonian Veterinary Review. Volume 44, Issue 1, Pages i-xii, e-ISSN 1857-7415, p-ISSN 1409-7621, DOI: 10.2478/macvetrev-2020-0032, 2021