SILVER NANOPARTICLES IN THE SOLUTION OF THE PROBLEM OF DRUG RESISTANCE IN MYCOBACTERIUM TUBERCULOSIS

Abstract

The goal — a scientific evaluation of the effectiveness and safety of NHS in the treatment of experimental drug-resistant tuberculosis. Materials and methods. Used silver nanoparticles obtained by an electrochemical method. With a size of 5-60 nm, 120-270 kontsentratsiey- 1 mcm² and the size of the stabilizer shell — 2-5 nm. 750 crops studied Inhibitory activity of the silver nanoparticles in an isolated form and as part of a nanocomposite with chemotherapy in concentrations of 5; 25 and 50 mcg/ml. Defines the minimum inhibitory concentration of bactericidal nanoparticles composed of a nanocomposite with isoniazid. To evaluate the morphometry M.tuberculosis used atomic force microscopy. Toxicology nanopreparations studied 83 non-linear white mice and 146 white rats. Chemotherapeutic Activity nanopreparations determined on an experimental model of tuberculosis in 65 white male mice imbrednoy line BALB/c. Infectivity dose amount 5х106 colony forming units injected into the sinus venosus animal eyes. Isoniazid, nanoparticles and nanocomposite began administered 14 days after infection by intramuscular injection daily. Treatment efficacy was determined by comparing the evaluation criteria in the experimental and control groups of animals. Evaluated the following indicators: survival index, body mass index and weight of target organ, lesions index, index smear and inoculation of affected organs. Conducted pathological examination. Results. When using isoniazid, which had resistant pathogens, with silver nanoparticles full and significant inhibition of the growth of the M.tuberculosis observed in 49,2% of cases. When the concentration of the nanoparticles 5 mcg/ml in the composite bactericidal activity reached 91,3%. The minimum inhibitory concentration of silver nanoperticles in combination with isoniazid was 2,5 mcg/ml, the minimum bactericidal — 5 mcg /ml. There have been changes in the M.tuberculosis morphometry under the influence of the nanocomposite according to atomic force microscopy. In the studied doses of isolated silver nanoparticles do not affect the basic biometrics, laboratory and functional parameters of the animals, and do not increase the toxicological parameters of isoniazid. All criteria studied the effectiveness of treatment of experimental tuberculosis had significantly priority performance using nanocomposite. Pathological studies have confirmed these results. Conclusions. Of the study provides a scientific rationale for the effectiveness of the experimental use of silver nanoparticles in treatment of drug-resistant tuberculosis. The most effective dose of silver nanoparticles in the composite in the treatment of experimental tuberculosis is 25 mcg / kg.