BackgroundDevelopment of biocompatible multifunctional polymeric drug carriers is crucial in modern pharmaceutics aimed to create “smart” drugs. The high potential of the PEGylated comb-like polymeric nanocarrier (PNC) in delivering both traditional and experimental drugs to tumor cells in vitro and in vivo has been demonstrated previously. In the present study, we investigated the general toxicity of polyethylene glycol (PEG) processed with both covalent and non-covalent attachments of PEG to compose a comb-like polymer that behaves like a simple chain of n monomers decorated with swollen side chains. The PNC possesses properties of a water-soluble surfactant containing methyl-terminated PEG side branches in some monomer units attached covalently to the carbon chain backbone.ResultsWe have demonstrated that the synthesized PNC possesses weak toxic effects toward human leukemia cells (HL-60 and Jurkat lines), as well as toward hepatocellular (HepG2), colon (HCT116) and breast (MCF-7) tumor cell lines. Additionally, after a long period (20 days) of intraperitoneal administration, the PNC had no significant toxic effects in laboratory white mice (470 mg/kg body mass in 1 ml) and Wistar rats (440 mg/kg body mass in 10 ml).ConclusionThe developed PNC we studied can be qualified as a compound of grade 4 toxicity (low toxicity substance). The reduced toxicity of this PNC in combination with its improved bioavailability and previously detected capability to enhance cytotoxicity toward tumor cells in vitro and potential tumor treatment effects in vivo suggests its potential as a safe drug delivery platform for treating various diseases, especially cancer.

The article presents the results of a study of the acute and subacute toxicity of the drug TILOTAR (a water-soluble powder for oral administration) made on the basis of tylosin tartrate. As a result of the research it was found that the drug "TILOTAR" refers to the 4th class of toxicity, that is, to low-toxic substances. After intragastric administration of the drug to white mice and rats at doses of 2500, 5000, 7500 mg/kg, all animals remained alive. Short-term inhibition was recorded in laboratory animals, which were given the drug at the maximum dose. Further changes in the clinical state of the animals of the experimental groups were not observed. The study of subacute toxicity of the drug "TILOTAR" showed that 14-day administration of a therapeutic dose of the drug leads to a decrease in erythropoiesis, the appearance of old forms of erythrocytes, damage to hepatocytes, the appearance of eosinophils, γglobulins, a decrease in protein biosynthesis, increased kidney function. The introduction of a 10-fold dose within 14 days reduced the body weight of the rats, leading to abnormalities in the liver and kidneys, and a decrease in the mass of the spleen. An increase in urea blood concentration and a decrease in creatinine may indicate impaired renal function in animals that were given a tenfold dose of the drug, and an increase in the level of α-and γ-globulins against the background of a decrease in body weight of rats indicates an overload of the body's immune system. In rats of the therapeutic group, homeostasis was maintained by enhancing kidney function, accompanied by a decrease in the number of erythrocytes due to young forms and the appearance of mature erythrocytes with a high level of hemoglobin (MCH), some destruction of hepatocytes (high level of alkaline phosphatase activity) while reducing the amount of albumin, an increase in relative levels of α-and γ-globulins. In the conducted experiments it was established that the macroscopic and microscopic structure of the internal organs of rats, while studying the subacute toxicity of the drug "TILOTAR", was preserved, no macroscopic changes were revealed. In rats receiving a 10-fold therapeutic dose of the drug for 14 days, focal protein dystrophy of the liver and kidneys was histologically established. 1 Державний науково-дослідний контрольний інститут ветеринарних препаратів та кормових добавок, м. Львів, Україна 2 ПрАТ "Технолог", м. Умань, Черкаська обл., Україна У статті наведені результати вивчення гострої та підгострої токсичності препарату "ТИЛОТАР" (водорозчинний порошок для перорального застосування), виготовленого на основі тилозину тартрату. У результаті проведених досліджень було встановлено, що препарат "ТИЛОТАР" належить до 4-го класу токсичності, тобто до малотоксичних речовин. Після внутрішньошлункового введення препарату білим мишам і щурам в дозах 2500, 5000, 7500 мг/кг всі тварини залишалися живими. Короткочасне пригні-

The article presents the study results of the acute and subacute toxicity of the veterinary drug “Tylmozyn 25” (solution for oral administration) based on tilmicosin. Intra-gastric administration of “Tylmozyn 25” to white mice at a dose of 25000 mg/kg of body weight caused the death of 100% of the animals, a dose of 15000 mg/kg of body weight caused the death of 66% of the white mice. The average time of death was 2 and 5 hours correspondingly. While determining the toxicity of “Tylmozyn 25” in white rats, we did not spot the death of any studied animal at any administered dose (5000, 15000, 25000 mg/kg of body weight). Based on the result of our study, we conclude that the veterinary drug Tylmozyn 25 belongs to the fourth of toxicity class – low toxic substances. LD50 of Tylmozyn 25 in white mice is 14167 mg/kg, while in white rats LD50 is higher than 25000 mg/kg. Testing on white rats intra-gastric drug “Tylmozyn 25” during for 14 days, both in therapeutic (80 mg/kg of body weight) and 10-fold doses (800 mg/kg of body weight) did not cause animal death, but caused a decrease in body weight, a significant decrease in the coefficients of weight of the liver and spleen and a tendency to increase the coefficients of weight of the heart and lungs compared with the animals of the control group. Animals which got the drug at a dose of 800 mg/kg of body weight showed erythrocytosis, leukopenia, increased enzymatic activity of AST, ALT, and LDH, the content of total protein against to decrease urea and creatinine, which may indicate impaired liver, kidney function and hematopoietic organs. The macroscopic and microscopic structure of the internal organs of the experimental rats is preserved. Rats receiving a tenfold therapeutic dose of the drug for 14 days, histologically revealed the most granular protein dystrophy in the liver and kidneys, which was manifested by discomplexation of the lamellae, presence of hepatocytes with uneven granular cytoplasm, slightly colored cytoplasm, hypertrophied nuclei, renal convoluted tubules and narrowing of their lumen, compaction of the mesh of the renal corpuscle. In the myocardium, the branching, swelling of the muscle fibers, swelling of the stroma with cell infiltrates, mainly of the lympho-histiocytic series, was observed, which indicated the development of serosa myocarditis. Structural changes in the liver, kidneys and heart were confirmed by biochemical parameters of the enzymatic activity of the serum of rats of this group.

To date, special attention should be paid to drugs that have antimicrobial, anti-inflammatory and wound-healing effects, one of which is sodium-containing drugs. The article presents the results of experimental studies to study the acute toxicity of sodium-containing drugs: glycetinate 2 %, its analogues – ovocid 2 %, ovocid 3 %, potassium-sodium 1.5% (Na/K 1.5 %). The study of acute toxicity of drugs was carried out by applying drugs to the skin of animals. The experiment used white rats weighing 250-270 g. 4 groups of rats with 3 animals in each were formed: rats of group I on the skin was applied ovocid 3 %, group 2 - Nа/К 1,5 %, 3rd group - ovocid 2 %, and the 4th group of rats (control) was applied glycetinate 2 %. The animals were subjected to clinical observations, assessing their general condition and skin reaction. The effect of drugs on morphological and biochemical parameters of blood of rats was studied. The studied drugs did not cause visible disorders of physiological functions, the appearance of clinical signs of intoxication. There were no significant clinical signs of inflammation or irritation (erythema, edema and cracks) on the skin of the animals, but there was a slight redness at the application site, which later disappeared. The studied sodium-containing preparations (ovocid 3 %, Nа/К 1,5 %, ovocid 2 %, glycetinate 2 %) under the conditions of a single application of the preparation to the skin of animals did not cause the death of animals, which allows us to classify these preparations as low-toxic substances.

The article presents the results of establishing the parameters of acute and subacute toxicity of the powder based on iodoform. Determination of acute toxicity parameters of the drug "Iodomin" were performed on 30 white mice 2-3 months of age, weighing 20-23 g and 30 white rats, aged 2-3 months, weighing 170-190 g. The drug was administered intragastrically, once, pre-dissolved in water. As a result of studies to determine acute toxicity by oral administration, it was found that, after administration of the drug in doses of 1000, 3000 and 5000 mg/kg, all animals remained alive. No changes in the clinical condition of the animals of the experimental groups were observed. The DL50 of ''Iodomin" powder is more than 5000 mg/kg. In conducted studies did not reveal the death of animals, respectively, the tested drug belongs to the IV class of toxicity (low toxicity). Studies on the determination of acute dermal toxicity of Iodomine were performed in accordance with the requirements of OECD № 402 (Acute Dermal Toxicity: Fixed Dose Procedure, 2017). Studies have shown that skin application of powder "Iodomin" at a dose of 2000 mg/kg body weight did not cause death, appearance of toxic effects. According to GHS the drug belongs to the 5th category. In the study of subacute toxicity, the drug was administered intragastrically, daily, pre-dissolved in water. On the 4th day of the experiment, in two experimental groups was a significant decrease in heart weight, which may be associated with functional load, and in group 2 (5-fold from therapeutic dose), along with that was a significant increase in liver mass, decreased concentration hemoglobin in the erythrocyte, creatinine in the blood, increased ALT activity. To determine the harmful effects of Iodomin powder on the mucous membrane of the eye were used 3 rabbits, to which the drug was administered in the amount of 2 drops in the conjunctival sac of the left eye. The harmful effect of the tested substance on the mucous membrane of the eyes was assessed by the appearance of hyperemia, edema and secretions according to the scoring system. When applying the suspension on the mucous membrane of the eye, it was found out, that after 24-48 hours the drug does not cause irritation. Also was found that the studied agent does not cause hyperemia, edema and changes in blood vessels. It's established that the powder "Iodomin" does not cause harmful effects on the mucous membranes of the eye.