In Vivo Study of Entero- and Hepatotoxicity of Silver Nanoparticles Stabilized with Benzyldimethyl-[3-myristoylamine)-propyl]ammonium Chloride (Miramistin) to CBF1 Mice upon Enteral Administration.

Silver nanoparticles (AgNPs) are the most widely studied antimicrobial nanomaterials. However, their use in biomedicine is currently limited due to the availability of data that prove the nanosilver toxicity associated primarily with oxidative stress development in mammalian cells. The surface modification of AgNPs is a potent technique of improvement of their biocompatibility. The synthetic or natural compounds that combine zero or low toxicity towards human and animal organisms with inherent antimicrobial properties are the most promising stabilizing agents, their use would also minimize the risks of microorganisms developing resistance to silver-based materials. We used a simple technique to obtain 30-60 nm AgNPs stabilized with benzyldimethyl[3-myristoylamine)-propyl]ammonium chloride monohydrate (BAC)-a well-known active ingredient of many antibacterial drugs. The objective of the study was to assess the AgNPs-BAC entero- and hepatotoxicity to CBF1 mice upon enteral administration. The animals were exposed to 0.8-7.5 mg/kg doses of AgNPs-BAC in the acute and to 0.05-2.25 mg/kg doses of AgNPs-BAC in the subacute experiments. No significant entero- and hepatotoxic effects following a single exposure to doses smaller than 4 mg/kg were detected. Repeated exposure to the doses of AgNPs-BAC below 0.45 mg/kg and to the doses of BAC below 0.5 mg/kg upon enteral administration also led to no adverse effects. During the acute experiment, the higher AgNPs-BAC dose resulted in increased quantities of aminotransferases and urea, as well as the albumin-globulin ratio shift, which are indicative of inflammatory processes. Besides, the relative mass of the liver of mice was smaller compared to the control. During the subacute experiment, the groups treated with the 0.25-2.25 mg/kg dose of AgNPs-BAC had a lower weight gain rate compared to the control, while the groups treated with the 2.25 mg/kg dose of AgNPs-BAC showed statistically significant variations in the blood serum transaminases activity, which indicated hepatosis. It should be noted that the spleen and liver of the animals from the groups treated with the 0.45 and 2.25 mg/kg dose of AgNPs-BAC were more than two times smaller compared to the control. In the intestines of some animals from the group treated with the 2.25 mg/kg dose of AgNPs-BAC small areas of hyperemia and enlarged Peyer's patches were observed. Histological examination confirmed the initial stages of the liver and intestinal wall inflammation.