In this study, we developed iron oxide nanoparticles stabilised with oleic acid/sodium oleate that could exert therapeutic effects for curing tumours via magnetic hyperthermia. A suspension of iron oxide nanoparticles was produced and characterised. The toxicity of the synthesised composition was examined in vivo and found to be negligible. Histological examination showed a low local irritant effect and no effect on the morphology of the internal organs. The efficiency of magnetic hyperthermia for the treatment of transplanted Walker 256 carcinoma was evaluated. The tumour was infiltrated with the synthesised particles and then treated with an alternating magnetic field. The survival rate was 85% in the studied therapy group of seven animals, while in the control group (without treatment), all animals died. The physicochemical and pharmaceutical properties of the synthesised fluid and the therapeutic results, as seen in the in vivo experiments, provide insights into therapeutic hyperthermia using injected magnetite nanoparticles.

Multilayer capsules of 4 microns in size made of biodegradable polymers and iron oxide magnetite nanoparticles have been injected intravenously into rats. The time-dependent microcapsule distribution in organs was investigated in vivo by magnetic resonance imaging (MRI) and ex vivo by histological examination (HE), atomic absorption spectroscopy (AAS) and electron spin resonance (ESR), as these methods provide information at different stages of microcapsule degradation. The following organs were collected: Kidney, liver, lung, and spleen through 15 min, 1 h, 4 h, 24 h, 14 days, and 30 days after intravenous injections (IVIs) of microcapsules in a saline buffer at a dosage of 2.5 × 10⁹ capsule per kg. The IVI of microcapsules resulted in reversible morphological changes in most of the examined inner organs (kidney, heart, liver, and spleen). The capsules lost their integrity due to degradation over 24 h, and some traces of iron oxide nanoparticles were seen at 7 days in spleen and liver structure. The morphological structure of the tissues was completely restored one month after IVI of microcapsules. Comprehensive analysis of the biodistribution and degradation of entire capsules and magnetite nanoparticles as their components gave us grounds to recommend these composite microcapsules as useful and safe tools for drug delivery applications.

Although new drug delivery systems have been intensely developed in the past decade, no significant increase in the efficiency of drug delivery by nanostructure carriers has been achieved. The reasons are the lack of information about acute toxicity, the influence of the submicron size of the carrier and difficulties with the study of biodistribution in vivo. Here we propose, for the first time in vivo, new nanocomposite submicron carriers made of bovine serum albumin (BSA) and tannic acid (TA) and containing magnetite nanoparticles with sufficient content for navigation in a magnetic field gradient on mice. We examined the efficacy of these submicron carriers as a delivery vehicle in combination with magnetite nanoparticles which were systemically administered intravenously. In addition, the systemic toxicity of this carrier for intravenous administration was explicitly studied. The results showed that (BSA/TA) carriers in the given doses were hemocompatible and didn’t cause any adverse effect on the respiratory system, kidney or liver functions. A combination of gradient-magnetic-field controllable biodistribution of submicron carriers with fluorescence tomography/MRI imaging in vivo provides a new opportunity to improve drug delivery efficiency.

Research in the development of new therapeutic agents with a wide spectrum of the antiviral activity and a low ability to develop resistance remains the main dimension in combating the global threat to public health. The need for a parenteral form of favipiravir was dictated by the necessity to increase the efficacy of therapy in COVID-19 inpatients. This dosage form has expanded the possibilities of drug therapy in the inpatients, for whom a therapeutic effect acceleration and a high safety profile of the drugs used are especially important.The aim of the article is the evaluation of the efficacy and safety of a medicinal product containing favipiravir for the parenteral administration against the background of pathogenetic and symptomatic therapy, in comparison with standard therapy in hospitalized COVID-19 patients.Materials and methods. An open, randomized, multicenter comparative study was conducted in 6 research centers in the Russian Federation to evaluate the efficacy and safety of favipiravir, a lyophilisate for the preparation of a concentrate for the infusion solution administrated to the patients hospitalized with COVID-19. Screening procedures and randomization were completed in 217 patients, 209 of which had completed the study in accordance with the protocol.Results. Between the study groups, statistically significant differences have been found out, making it possible to consider the hypothesis of the drug Areplivir (favipiravir) superiority for the parenteral administration over the standard therapy, which included favipiravir (p. o.) and remdesivir. A comparative analysis has shown that a course of therapy with the parenteral favipiravir drug leads to a significant improvement in the condition of patients with COVID-19, significant benefits in terms of the speed and frequency of improvement in the clinical status of patients, as well as a reduction in the hospital stay length. It has been proven that therapy with a drug containing favipiravir for the parenteral administration does not adversely affect the parameters of clinical and biochemical blood tests, urinalysis, coagulograms, vital signs and ECG, which indicates the therapy safety. The study drug is characterized by a high safety profile and tolerability.Conclusion. The versatility and resistance to mutations of RNA-dependent RNA polymerase make it possible to consider it as the main target for combating the most common RNA viruses that cause ARVI, that determines the need further studies of favipiravir to expand the range of its indications.

The aim of the study is to assess the efficacy and safety of the Favipiravir (Areplivir) drug, compared to the standard etiotropic therapy in the patients hospitalized with COVID-19.Material and methods. The research was conducted as a part of an open, randomized, multicenter comparative study of the efficacy and safety of Areplivir, 200 mg film-coated tablets (“PROMOMED RUS” LLC, Russia), in the patients hospitalized with COVID-19. The dosing regimen of Favipiravir was 1600 mg twice a day on the 1^st day and 600 mg twice a day on days 2–14. Thirty nine patients were enrolled into the study with a laboratory-established diagnosis of a new type of Coronavirus infection caused by SARS-CoV-2 (confirmed) of moderate severity, with pneumonia. The group of comparison (22 patients) received standard etiotropic therapy, prescribed in accordance with the current version of the temporary guidelines for the diagnosis and treatment of COVID-19, represented mainly by Hydroxychloroquine with the dosage regimen of 800 mg on the 1^st day, then 400 mg on days 2–7, and Azithromycin 500 mg once a day for 5 days. The main group (17 patients) received Favipiravir (Areplivir) as etiotropiс therapy.Results. In the main group, the time period until fever disappeared was found to be 1.36 days shorter than in the group of comparison (p<0.05); there was a higher rate of the reduction of inflammatory changes in the lungs according to the computer tomography data (38.4% vs 14.9%, p<0.05). By the end of the treatment, there was also a lower lactate level in the blood (27.1%, p<0.05) than in the patients of the group of comparison. The evaluation of the drug efficacy ассording to the Categorical Ordinal Scale of Clinical Improvement and measurements of oxygen saturation in the blood, manifested similar positive dynamics in the patients treated ассording to various etiotropic therapy regimens. By the end of the treatment, the RNA SARS-CoV-2 tests were also negative in all the patients. As for the overall frequency of adverse events (AEs), no relevant distinctions were found between the groups. A greater part of AEs was related to hepatotoxicity, with a predominantly clinically relevant increase in alanine aminotransferase (ALT). A clinically relevant prolongation of the corrected QT interval on the standard ECG was found to occur in the standard-therapy group on day 5, while no serious AEs were registered in the main group. No serious adverse reactions were registered in patients of the main group.Conclusion. The efficacy of the Favipiravir (Areplivir) therapy for the novel coronavirus infection has proved to be superior to the efficacy of the standard etiotropic therapy in a number of aspects. Basing on the obtained findings, Favipiravir (Areplivir) drug can be recommended for treating patients with the novel coronavirus infection of moderate severity.