ORIGINAL_ARTICLE 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. https://macvetrev.mk/Files/Article/2021/10.2478/macvetrev-2020-0032/macvetrev-2020-0032.pdf 2021-03-15T09:00:00 17 28 10.2478/macvetrev-2020-0032 silver nanoparticles skin burns silver ointment skin healing infected burns Mukhallad Abdul Kareem Ramadhan mukalad.mcm@uomisan.edu.iq false 1 Department of Pathology, College of Medicine, University of Misan, Misan, Iraq LEAD_AUTHOR Abbas Najee Balasm false 2 Department of Pathology, College of Medicine, University of Misan, Misan, Iraq AUTHOR Sanaa Basheer Kadhm false 3 Department of Microbiology, College of Medicine, University of Misan, Misan, Iraq AUTHOR Haider Faleh Al-Saedi false 4 Department of Pharmacology and Toxicology, College of Pharmacy, University of Al-Ameed, Karbala, Iraq AUTHOR 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. PMid:24823434 PMCid:PMC4684260 1 10.2217/nnm.14.40 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. 2 10.3389/fmats.2016.00027 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. PMid:19473014 3 10.1021/mp900056g 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. PMid:23455461 PMCid:PMC3634485 4 10.3390/ijms14034817 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. 5 10.1016/S0305-4179(99)00116-3 Klasen, H.J. (2000). Historical review of the use of silver in the treatment of burns. I. Early uses. Burns 26(2): 117-130. 6 10.1016/S0305-4179(99)00108-4 Hussain, S., Ferguson, C. (2006). Best evidence topic report. Silver sulphadiazine cream in burns. Emerg Med J. 23(12): 929-932. PMid:17130603 PMCid:PMC2564257 7 10.1136/emj.2006.043059 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. PMid:17538258 8 10.1097/01.ASW.0000276415.91750.0f 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. PMid:17651232 9 10.1111/j.1742-481X.2007.00338.x Fong, J., Wood, F. (2006). Nanocrystalline silver dressings in wound management: a review. Int J Nanomedicine. 1(4): 441-449. PMid:17722278 PMCid:PMC2676636 10 10.2147/nano.2006.1.4.441 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. PMid:17244325 11 10.1111/j.1524-475X.2006.00190.x 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. PMid:16242655 PMCid:PMC3071678 12 10.1016/j.chembiol.2005.08.014 Robins, E.V. (1990). Burn shock. Crit Care Nurs Clin North Am. 2(2): 299-307. 13 10.1016/S0899-5885(18)30830-X 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. PMid:20429870 PMCid:PMC2935806 14 10.2174/157489110791233522 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. 15 10.1016/j.jksus.2010.06.006 Cordeiro, M.F. (2002). Beyond mitomycin: TGF-beta and wound healing. Prog Retin Eye Res. 21(1): 75-89. 16 10.1016/S1350-9462(01)00021-0 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. PMid:25538469 PMCid:PMC4268627 17 10.4103/0976-0105.145776 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. PMid:17075952 18 10.1002/cmdc.200600171 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. PMid:17906429 19 10.1097/01.ASW.0000294757.05049.85 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. PMid:18550449 20 10.1016/j.nano.2008.04.006 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. PMid:12100375 21 10.1046/j.1524-475X.2002.10308.x 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. PMid:17175106 22 10.1016/j.burns.2006.06.020 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. 23 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. 24 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. 25 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. 26 10.1016/S0580-9517(08)70618-4 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. PMid:22884902 PMCid:PMC3878450 27 10.1016/j.bbi.2012.07.013 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. PMid:23261214  28 10.1016/j.biomaterials.2012.11.035 Reed, L.J., Muench, H. (1938). A simple method of estimating fifty percent endpoints. Am J Hyg. 27(3): 493-497. 29 10.1093/oxfordjournals.aje.a118408 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. 30 10.1515/macvetrev-2015-0065 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. 31 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. PMid:9144730 32 10.1023/A:1012091231023 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. 33 10.1016/j.physe.2004.10.014 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. 34 10.1088/0957-4484/18/22/225103 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. PMid:23466321 35 10.1016/j.saa.2013.01.049 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. 36 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. PMid:28874692 PMCid:PMC5585259 37 10.1038/s41598-017-10481-0 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. PMid:12954584 38 10.1093/annonc/mdg374 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. PMid:24726122 39 10.1016/j.jpedsurg.2013.12.012 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. PMid:18771884 40 10.1016/j.jvs.2008.06.042 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. PMid:26952588 41 10.5301/jabfm.5000268