Benzyldimethyl[3-(miristoylamino)-propyl]ammonium chloride stabilized silver nanoparticles (Argumistin™) in medicine: results of clinical trials for treatment of infectious diseases of dogs and perspectives for humans

Yurii Krutyakov 1 , 2 , Alexey Klimov 1 , Boris Violin 3 , Vladimir Kuzmin 4 , Victoria Ryzhikh 5 , Alexander Gusev 6 , 7 , Olga Zakharova 8 ,  and George Lisichkin 1
  • 1 Lomonosov Moscow State University, Department of Chemistry, 1 Lenin Hills, Moscow, 119991, Russia
  • 2 National Research Center “Kurchatov Institute”, 1 Academician Kurchatov Square, Moscow, 123182, Russia
  • 3 All-Russian State Center for Quality and Standardization of Veterinary Drugs and Feed, 5 Zvenigorodskoe highway, Moscow, 123022, Russia
  • 4 Saint-Petersburg State Academy of Veterinary Medicine, 5 Chernigovskaya Street, Saint-Petersburg, 196084, Russia
  • 5 Grand Harvest Research International Development Ltd., 7 Ronda Doctor Turró, 9-B, Mataró, 08303, Barcelona, Spain
  • 6 Derzhavin’s Tambov State University, 33, Internatsionalnaya Street, Tambov, 392000, Russia
  • 7 National University of Science and Technology “MISIS”, 4, Lenin Avenue, Moscow, 119991, Russia
  • 8 Deputy Director of Research Institution for Ecology and Biotechnology Derzhavin’s Tambov State University, 33, Internatsionalnaya Street, Tambov, Russia, Phone: +7 961 618 9379
Yurii Krutyakov
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  • Yurii Krutyakov, MS, PhD, is Head of the Laboratory of Functional Nanomaterials for Agriculture, Department of Chemistry, Lomonosov Moscow State University (MSU). He graduated from the MSU in 2005 and obtained his PhD degree in Colloid and Interface Science in 2008. His research interests lie in the area of design and creation of new plant protection products and fertilizers containing nanomaterials as active components, development of nanosilver based antibacterial and anti-inflammatory veterinary drugs against infectious diseases of agricultural and small animals.
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, Alexey Klimov
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  • Alexey Klimov is a member of the development team of an antiseptic drug with a wound healing effect for animals and a crop protection agent widely used in Russia. He graduated from the Moscow State University in 2011. He is the author of several publications on the topic of colloidal chemistry and physics. He has participated in conferances on colloidal and physical chemistry and quantum optics.
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, Boris Violin
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  • Boris Violin, PhD graduated from the Moscow Veterinary Academy in 1978. His professional field includes quality assurance and standardization of pharmaceutical drugs. His research interests lie in the area of veterinary pharmacology and toxicology and the development of new pharmaceutical formulations, primarily, drugs for animal infectious diseases treatment. Has over 180 publications on the topic of veterinary pharmacology and toxicology.
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, Vladimir Kuzmin
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  • Vladimir Kuzmin graduated from the Leningrad Veterinary Institute in 1976. He obtained his doctoral degree in Veterinary Science in 1995. His research interests are broad and cover planning of preventive and curative measures for different animal diseases; epizootic monitoring; studying of novel pharmaceutical drugs for animal treatment, etc. he is the author of over 170 publications and holds five patents.
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, Victoria Ryzhikh
  • Spain
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  • Victoria Ryzhikh has a in Membrane Technology. She is a senior researcher and international certification manager of Grand Harvest Research International Development Ltd. Her research interests include physical chemistry of polymers, membrane technology and nanotechnology and nanomaterials. She is the author of several publications on the physical chemistry of polymers.
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, Alexander Gusev
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  • Alexander Gusev, PhD is the director of the Research Institution for Ecology and Biotechnology, Derzhavin’s Tambov State University, Tambov, Russia; he is assistant Professor in NUST “MISiS”, Moscow, Russia. His research interests include nanobiointeractions and nanotoxicology of carbon, metallic and oxide nanoparticles. He has published over 30 peer reviewed articles, over 50 conference proceedings, textbooks, and holds two patents.
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, Olga Zakharova
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  • Olga Zakharova is a specialist in environmental science, she is Deputy Director of Research Institution for Ecology and Biotechnology, Derzhavin’s Tambov State University, Tambov, Russia. Her research interests lie in the field of antibacterial nanomaterials and recycling of nanodispersed wastes. She has published 13 peer reviewed articles, over 20 conference proceedings, textbooks, and holds one patent.
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and George Lisichkin
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  • George Lisichkin is Head of the Laboratory of Surface Chemistry, Department of Chemistry, Moscow State University (MSU). He graduated from the MSU in 1964. He obtained his doctoral degree in Chemical Science in 1982. His research interests include surface chemistry, heterogenic catalysis, chemistry of marine environment and problems in chemical education. He is the author of over 300 publications and over 70 inventions.
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Abstract

Increased interest in nanosilver during the last 10 years is mainly explained by the emergence and spread of pathogenic microorganisms with multiple drug resistance, including resistance to last-generation antibiotics. In this article, we for the first time, give a description of large-scale clinical trials of a new nanosilver based antibacterial drug [containing two active components: silver nanoparticles (AgNPs) (10–50 ppm) and benzyldimethyl[3-(miristoylamino)-propyl]ammonium chloride (100 ppm)] registered in Russia in 2015 as a veterinary drug under the brand name Argumistin™. This drug has been approved for application in a diluted dosage form – as eye drops, intranasal drops and orally; it has also been approved for application in a more concentrated dosage form (up to 50 ppm of nanosilver) as ear drops and as an antiseptic during demodicosis and gum disease treatment, open wound treatment, etc. We have registered the high therapeutic effectiveness of Argumistin™ during treatment of infectious conjunctivitis, gingivitis, parodontosis and enteritis of dogs. Application of this antibacterial drug gives considerable (up to 70% in case of periodontal diseases) reduction in the treatment period and prevention of complications. The results of clinical trials in the treatment of infectious diseases of dogs makes Argumistin™ a promising candidate for an effective antibacterial drug for human medicine.

  • 1.

    Brennan S, Leaper D. The effect of antiseptics on the healing wound: a study using the rabbit ear chamber Br J Surg 1985;72:780–2.

    • Crossref
    • PubMed
    • Export Citation
  • 2.

    Baggot J. Antimicrobial selection, administration and dosage. J South Afr Vet A 1998;69:174–85.

  • 3.

    Ortuño A, Scorza V, Castellà J, Lappin M. Prevalence of intestinal parasites in shelter and hunting dogs in Catalonia, Northeastern Spain. Vet J 2014;199:465–7.

    • Crossref
    • PubMed
    • Export Citation
  • 4.

    Martins C, Barros C, Bier D, Marinho A, Figueiredo J, Hoffmann J, et al. Dog parasite incidence and risk factors, from sampling after one-year interval, in Pinhais. Brazil Rev Bras Parasitol Vet. 2012;21:101–6.

    • Crossref
    • Export Citation
  • 5.

    Berset-Istratescu C, Glardon O, Magouras I, Frey C, Gobeli S, Burgener I. Follow-up of 100 dogs with acute diarrhoea in a primary care practice. Vet J. 2014;199:188–90.

    • Crossref
    • Export Citation
  • 6.

    Chatzopoulos D, Athanasiou L, Spyrou V, Fthenakis G, Billinis C. Rotavirus infections in domestic animals. J Hellenic Vet Med Soc 2013;64:145–60.

  • 7.

    Truszczyński M, Posyniak A, Pejsak Z. Mechanisms of the emergence of resistance against the action of antibiotics and disinfectants in bacteria. Med Wet 2013;69:131–5.

  • 8.

    Scott W. Antimicrobial resistance: time for action. Vet Rec 2011;169:122–3.

  • 9.

    Samson-Himmelstjerna G, Blackhall W. Will technology provide solutions for drug resistance in veterinary helminths? Vet Parasitol 2005;132:22339.

    • Crossref
    • PubMed
    • Export Citation
  • 10.

    Morley P, Apley M, Besser T, Burney D, Fedorka-Cray P, Papich M, et al. Antimicrobial drug use in veterinary medicine. J Vet Int Med 2005;19:617–29.

    • Crossref
    • Export Citation
  • 11.

    Persoons D, Hoorebeke S, Hermans K, Butaye P, Kruif A, Haesebrouck F, et al. Methicillin-resistant Staphylococcus aureus in poultry. Emerg Infect Dis 2009;15:452–3.

    • Crossref
    • PubMed
    • Export Citation
  • 12.

    Krutyakov Yu, Kudrinskiy A, Olenin A, Lisichkin G. Synthesis and properties of silver nanoparticles: advances and prospects. Russ Chem Rev 2008;77:233–57.

    • Crossref
    • Export Citation
  • 13.

    Credé C. Die Verhütung der Augenentzündung der Neugeborenen (“Prevention of inflammatory eye disease in the newborn”). Arch Gynäkol 1881;17:50–3.

  • 14.

    Burrell R. A scientific perspective on the use of topical silver preparations. Ostomy Wound Manage 2003;49(5A Suppl):19–24.

    • PubMed
    • Export Citation
  • 15.

    Klasen H. A Historical review of the use of silver in the treatment of burns. II. Renew Interest for silver. Burns 2000;26:131–8.

    • Crossref
    • Export Citation
  • 16.

    Gupta A, Maynes M, Silver S. Effects of halides on plasmid-mediated silver resistance in Escherichia coli. Appl Environ Microbiol 1998;64:5042–5.

    • Crossref
    • PubMed
    • Export Citation
  • 17.

    Matsumura Y, Yoshikata K, Kunisaki S, Tsuchido T. Mode of bactericidal action of silver zeolite and its comparison with that of silver nitrate. Appl Environ Microbiol 2003;69:4278–81.

    • Crossref
    • PubMed
    • Export Citation
  • 18.

    Morones JR, Elecheguerra JL, Camacho A, Holt K, Kouri JB, Ramirez JT, et al. The bactericidal effect of silver nanoparticles. Nanotechnology 2005;16:2346–53.

    • Crossref
    • PubMed
    • Export Citation
  • 19.

    Raffi M, Hussain F, Bhatti TM, Akhter JI, Hameed A, Hasan MM. Antibacterial characterization of silver nanoparticles against E. coli ATCC-15224. J Mater Sci Technol 2008;24:192–6.

  • 20.

    De Souza A, Mehta D, Leavitt RW. Bactericidal activity of combinations of Silver-Water Dispersion™ with 19 antibiotics against seven microbial strains. Curr Sci 2006;91:926–9.

  • 21.

    Li P, Wu C, Wu Q, Li J. Synergetic antibacterial effects of b-lactam antibiotic combined with silver nanoparticles. Nanotechnology 2005;16:1912–17.

    • Crossref
    • Export Citation
  • 22.

    Vertelov G, Krutyakov Yu, Efremenkova O, Olenin A, Lisichkin G. A versatile synthesis of a highly bactericidal Myramistin® stabilized silver nanoparticles. Nanotechnology 2008;19:1–7.

  • 23.

    Bolyakhina SA, Nasartdinova GF, Donchenko NA, Korobkova EA, Denisov AN, Krutyakov YuA. Acute and chronic toxity of the veterinary drug Argumistin. Sib Bull Agric Sci 2014;3:95–101. (in Russian).

  • 24.

    Koptev VYu. Embriotoxicity and teratogenicity study of Argumistin preparation when administered orally. Study report. Novosibirsk 2014:12. (in Russian).

  • 25.

    Kuzmin VA. Immunotoxicity study of veterinary preparation Argumistin when consumed orally. Study report. Saint-Petersburg 2014:20. (in Russ.)

  • 26.

    Andreeva NL. Carcinogenity study of veterinary preparation Argumistin. Study report. Saint-Petersburg 2014:18. (in Russsian).

  • 27.

    Andreeva NL. Miramistin pharmacokinetics study in mice tissues and organs after oral administration of veterinary preparation Argumistin. Study report. Saint-Petersburg 2014:14. (in Russian).

  • 28.

    Andreeva NL. Miramistin residues evaluation in chicken tissues and organs after oral administration of veterinary preparation Argumistin. Study report. Saint-Petersburg 2014:13. (in Russian).

  • 29.

    Andreeva NL. Miramistin residues evaluation in cow milk, tissues and organs after intercisternal and intrauterine application of veterinary preparation Argumistin. Study report. Saint-Petersburg 2014:19. (in Russian).

  • 30.

    Demling RH, Leslie DeSanti MD. The rate of re-epithelialization across meshed skin grafts is increased with exposure to silver. Burns 2002;28:264–6.

    • Crossref
    • PubMed
    • Export Citation
  • 31.

    Lansdown ABG, Silver 2: toxicity in mammals and how its products aid wound repair. J. Wound Care 2002;11:173–7.

    • Crossref
    • PubMed
    • Export Citation
  • 32.

    Lansdown ABG. Metallothioneins: potential therapeutic aids for wound healing in the skin. Wound Repair Regen 2002;10:130–2.

    • Crossref
    • PubMed
    • Export Citation
  • 33.

    Nadworny PL, Wang J, Tredget EE, Burrell RE. Anti-inflammatory activity of nanocrystalline silver in a porcine contact dermatitis model. Naomed Nanotechnol Biol Med 2008;4:241–251.

    • Crossref
    • Export Citation
  • 34.

    Bhol KC, Schechter PJ. Topical nanocrystalline silver cream suppresses inflammatory cytokines and induces apoptosis of inflammatory cells in a murine model of allergic contact dermatitis. Br J Dermatol 2005;152:1235–42.

    • Crossref
    • Export Citation
  • 35.

    Wright JB, Lam K, Buret AG, Olson ME, Burrell RE. Early healing events in a porcine model of contaminated wounds: effects of nanocrystalline silver on matrix metalloproteinases, cell apoptosis, and healing. Wound Repair Regen 2002;10:141–51.

    • Crossref
    • Export Citation
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The European Journal of Nanomedicine is dedicated to basic and clinical research in Nanomedicine. Its focus lies on the clinical application of nanoscience tools, methods and materials and on the exploration of the implications of Nanomedicine. EJNM covers topics from nano(bio)technological engineering and characterization to clinically translatable innovative prevention, diagnostics, and therapies of major as well as neglected human diseases.

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