PRECLINICAL STUDIES OF COPPER NANOPARTICLES
DOI:
https://doi.org/10.11603/mcch.2410-681X.2020.v.i3.11546Keywords:
Cuprum nanoparticles, preclinical study, biosafety, toxicity, antimicrobial action, fungicidal actionAbstract
Introduction. Preclinical study of drugs is an integral part of the drug creation process. Established for the results of preclinical studies, the characteristics of specific pharmacological activity and harmfulness during use and its possible long-term consequences are the main factors that determine the possibility of transferring the drug to commercial release and the feasibility of its medical use.
The aim of the study – to learn the biosafety, acute toxicity, antimicrobial and fungicidal effects of copper nanoparticles.
Research Methods. The biosafety of the synthesized substance of nanoparticles in in vitro tests was determined using cytotoxicity, mutagenicity, molecular genetic (genotoxicity), physiological ("state of the microflora of the human gastrointestinal tract") and biochemical (ATP-ase and lactate activity). Antimicrobial and fungicidal properties of drug were also studied in clinical isolates of infectious and inflammatory pathogens: bacteria S. aureus, E. coli, Proteus mirabilis, K. pneumoniae, Enterobacter aerogenes, P. aeruginosa, fungi of the genus Candida – C. albicans, Candida non-albicans and other micromycetes – Penicillium spp., Paecilomyces lilacinus, A. niger and A. flavus.
Results and Discussion. The interaction of copper nanoparticles with test eukaryotic cells did not lead to the appearance of primary DNA damage, compared with the effect of N-nitrosomethylurea, which is a known genotoxicant. In the samples of test eukaryotic cells of the line treated with copper nanoparticles in a wide concentration range, no cytotoxic effect of the studied nanomaterial was recorded. The experimental substance of copper nanoparticles (CuNP) has a pronounced antimicrobial and fungicidal activity against all studied pathogenic test cultures: both in the initial concentration (32.0 mg/ml for metal) and for its tenfold dilution (3.2 mg/ml in conversion to metal). Complete inhibition of the growth of pathogenic test strains was observed at final inoculation doses of microorganisms on plates from 103 to 105 CFU/cm3. The studied substance of copper nanoparticles also showed antimicrobial and fungicidal action against clinical isolates of pathogens of infectious and inflammatory processes of different localization, namely bacteria and fungi.
Conclusion. Evaluation of acute toxicity of copper nanoparticle substances after a single intravenous injection of white rats depending on the dose level in the range of 14 days of observation allows to cancel the substance of copper nanoparticles up to class IV toxicity (low toxicity).
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