PRECLINICAL STUDY OF IRON NANOPARTICLES

Abstract

Introduction. Preclinical studies of drugs is an integral part of the drug development process. Preclinical research is the longest and most responsible stage of drug creation, which requires special approaches to planning and quality assurance in the planning of measurement experiments, testing and evaluation of its results.

The aim of the study – to determine 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 (ATPase and lactate activity). Antimicrobial activity zerovalent Iron (Fe⁰NP) for test strains of microorganisms was determined by the method of serial dilutions in broth according to methodical instruction 4.2.1890-04, 2004. The following test strains of microorganisms were used: Salmonella typhimurium, Shigella sonnei, Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Proteus mirabili, Candida albicans from the collection of the State Research and Control Institute of Biotechnology and strains of microorganisms.

Results and Discussion. The synthesized nanoparticles are particles of Fe⁰NP. The interaction of the synthesized iron nanoparticles with the 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. The synthesized nanoparticles were characterized as biosafe in mutagenicity tests using polychromatophilic erythrocytes of animal bone marrow. The analysis showed that the experimental substance Fe⁰NP in the studied concentration range showed moderate antimicrobial activity in in vitro tests against both gram-negative (S. typhimurium, S. sonnei, P. aeruginosa, P. vulgaris, P. mirabilis), and gram-positive microorganisms (S. aureus). However, fungi Candida albicans were insensitive to iron nanoparticles at the studied concentrations.

Conclusions. Physico-chemical characteristics and evaluation of biosafety criteria in in vitro and in vivo tests indicate that the synthesized spherical nanoparticles of zerovalent iron are characterized by a low level of potential danger: no genotoxic, cytotoxic, mutagenic effects, adverse effects on key biochemical parameters state of a living organism. This allows us to recommend the synthesized substance of iron nanoparticles for further research with a view to their use as a potential biologically active substance.