ДОСЛІДЖЕННЯ ГОСТРОЇ ТОКСИЧНОСТІ КОН'ЮГАТУ НАНОЧАСТИНОК МІДІ З ЦЕФТРІАКСОНОМ ПРИ ВНУТРІШНЬОШЛУНКОВОМУ ВВЕДЕННІ МИШАМ

Анотація

ACUTE ORAL TOXICITY TESTING OF THE COPPER NANOPARTICLE-CEFTRIAXONE CONJUGATE IN MICE

P.V. Simonov

Bogomolets National Medical University, Kyiv

Summary: The antimicrobial resistance of causative agents of infectious diseases problem may be solved by an introduction of medications based on metal nanoparticles and their combinations with other antimicrobial drugs into medical practice. The results on a determination of the copper nanoparticle-ceftriaxone conjugate acute toxicity parameters in an experiment of oral administration in BALB/с mice were presented in the article. It had been found out that the studied substance belonged to the 5^th toxicity class (practically non-toxic). Central and autonomous nervous systems, gastro-intestinal tract and kidneys were the biological targets of action of the copper nanoparticle-ceftriaxone conjugate after oral administration in mice. A reversibility of the studied substance’s negative influence on animals was confirmed by an absence of significant influence on a dynamics of body mass changes. It seems advisable to continue studies on the copper nanoparticle-ceftriaxone conjugate in order to introduce it into medical practice for a treatment of infections, particularly those caused by antimicrobial resistant strains.

Key words (MeSH Terms): Metal Nanoparticles; Copper; Ceftriaxone; Safety; Toxicity Tests, Acute; Administration, Oral; Mice.

Introduction. The antimicrobial resistance of causative agents of community- and hospital-acquired infections is a global healthcare problem nowadays. It may be solved by an introduction of new antimicrobial medications, which are effective against resistant strains of bacteria and fungi, into medical practice. Copper-based nanoparticles may become such novel drugs.

It seems advisable to develop a medication based on the copper nanoparticle-ceftriaxone conjugate. It would comprise a composition of a safe and efficient cephalosporin antibiotic with copper, which is an essential trace element for a human organism and possesses wide spectrum of antimicrobial action, especially in a nanostructured form.

The purpose of this study was to determine acute oral toxicity parameters of the copper nanoparticle-ceftriaxone conjugate in laboratory female BALB/с mice.

Methods. Pharmacological, toxicological, pathomorphological, and statistical methods were used to achieve the goals and objectives of the study.

Results and discussion. The conjugate consisting of 20 nm chemically stable spherical zerovalent copper nanoparticles, obtained by original protocol of chemical condensation in aqueous solution method, and ceftriaxone, a third generation cephalosporin, belongs to the 5^th toxicity class (practically non-toxic) according to K. K. Sidorov classification in an experiment of single oral administration in laboratory female BALB/с mice.

Central and autonomous nervous systems, gastro-intestinal tract and kidneys are the biological targets of action of the copper nanoparticle-ceftriaxone conjugate after oral administration in mice.

A reversibility of the copper nanoparticle-ceftriaxone conjugate’s toxic influence on animals after single oral administration is confirmed by an absence of significant influence on a dynamics of body mass changes.

Conclusions. The copper nanoparticle-ceftriaxone conjugate appears to be a safe substance after single oral administration in laboratory female BALB/с mice, according to results obtained. It seems advisable to continue studies on the substance in order to introduce it into medical practice for a treatment of infections, particularly those caused by antimicrobial resistant strains.