Targeting is a phenomenon in which the distribution of a drug in the body occurs in such a way that the main part of it interacts with the target tissue at the cellular or subcellular level to achieve the desired pharmacological effect on the selected site without undesirable interactions in other organs. This can be achieved using a drug delivery system such as niosomes, which are non-ionic vesicles of surfactants obtained by hydrating synthetic non-ionic surfactants with the inclusion of cholesterol. They are vestibular systems similar to liposomes that can be used as carriers of amphiphilic or lipophilic drugs. Niosomes are a promising drug delivery tool, and it has been widely evaluated as a possibility of controlled release and targeted delivery of the active substance for the treatment of cancer, autoimmune diseases, viral and other infectious diseases. It can be assumed that encapsulation of the drug in the vesicular system prolongs its presence in the systemic circulation and increases the possibility of penetration into the target tissue, possibly reducing toxicity if selective absorption can be achieved.
The article presents the results of studying the physicochemical properties of exosome preparations obtained by ultrafiltration, which indicate a high degree of the composition and properties dependence of the obtained product on the material of the filters used. Quantitative determination of proteins and nucleic acids in exosome samples using UPN-50 filters allows us to conclude that the content of the main impurity compounds in the preparation is significantly reduced compared to dispersions obtained using filters with pore sizes of 220 and 450 nm. Analysis of flow cytometry data made it possible to demonstrate that when using the UPN-50 filter, an increase in the contribution to the dispersion of all types of fractions of non-exosomal size was observed, the appearance of which can result from fraction destruction associated with pore size or filter material properties. drying of the dispersion was observed in the studied exosome samples. Fraction sizes ranged from 40 to 450 nm (an average of about 200 nm). Exosomes from the entire variety of membrane vesicles are fractions that have the most suitable characteristics that allow them to be used as a nanoscale drug delivery vehicle while ensuring the necessary quality control of the drug at the sample preparation stage.
One of the main promising directions in the development of pharmacology is the development of selective drugs and effective approaches to their production using nanoscale drug delivery vehicles. Providing the necessary therapeutic concentration of drugs in target cells is not an easy task. To solve it, a specific drug carrier is required. The most promising is the use of biodegradable delivery systems, due to the lack of the need to use expensive equipment, and it is also possible to synthesize them in production volumes. The need to develop systems for the controlled delivery of drugs, especially antibacterial drugs, is due to their clear advantage over antibiotics in standardized dosage forms. Increasingly, in poultry industry, high mortality rates of chickens began to be observed in the acute form of enterotoxemia due to Clostridium perfringens and its associations with another microflora. The aim of this paper is to study the therapeutic efficacy of a free and included in biodegradable system antibacterial drug (cefotaxime) for bacterial infections in birds. There were formed 3 experimental and 1 control group of broiler chickens of the cross Cobb-500 daily age of 15 animals each. At the age of 10 days, the birds of group 1-3 were orally infected with virulent diurnal cultures of microorganisms: Clostridium perfringens. During the experiment, daily monitoring of the general condition and behavior of the birds, consumption of feed and water was carried out, the clinical status of the sick birds, the time of onset of positive dynamics and the time of recovery were evaluated. After completing the course of therapy, monitoring of the state of the birds continued for 7 days. After completion of the experiment, bacteriological examination showed that the use of cefotaxime at a dose of 10 mg/kg for 7 days does not eradicate Clostridium perfringens, while the use of cefotaxime based on chitosan and cefotaxime based on exosomes at a dose of 10 mg/kg provides 100% therapeutic efficiency.
One of the main promising directions in the development of pharmacology is the development of drugs that provide targeted drug concentration and effective approaches to obtaining them using nanoscale drug delivery systems. In our opinion, the most promising is the use of biodegradable delivery systems due to their low toxicity and xenobiotic effects on the patient’s body. The need to develop regulated drug delivery systems is due to their clear advantage over analogues in standardized dosage forms. Based on modern research publications we have developed an exosomal antibacterial form of azithromycin that has pronounced selective properties for respiratory epithelial cells. The aim of the work was to study the safety parameters of the developed drug based on exosomal particles, in particular subchronic toxicity. For the study 3 experimental and 1 control groups of white rats weighing 190-220 g were formed with 10 heads each. The drug was administered intragastrically daily for 90 days in doses of 1/10; 1/20 and 1/50 of the LD50 set in the acute experiment. The study found that the use of the developed exosomal drug intragastrically once a day for 90 days does not affect the behavioral responses of animals and their external condition.
Each drug, before being introduced to the pharmaceutical market, undergoes a mandatory set of preclinical and clinical studies, including those for allergenicity. As a result of the work carried out from 2015 to 2020 at the Department of Therapy and Pharmacology, selective preparations based on exosomal (Exazit) and chitosan (Chitasit) nanoparticles have been developed, and their physicochemical and pharmacological and therapeutic properties have been analyzed. This article presents the results of studying the allergenic and irritating properties of these drugs. To study the allergic effect after oral administration of drugs, 6 experimental and 6 control groups of guinea pigs weighing 250–300 g were formed. Testing of the sensitizing properties of drugs was carried out on days 10, 15 and 30 from the start of administration. The results of the conducted studies have established that the conjunctival test of sensitized guinea pigs, throughout the experiment, did not differ from the reaction in control animals. During a visual assessment of the state of the conjunctiva, cornea and eyelids of the eyes of experimental animals, it was found that the studied drugs did not cause irritation of the conjunctiva both immediately after instillation and throughout the entire experiment. The setting of the provocative nasal test did not cause hyperemia of the mucous membrane, sneezing and increased mucus secretion in animals. The percentage of degranulated mast cells in the experimental groups is less than 10%. Thus, as a result of the study of the allergenic properties of Exazit and Chitasit in guinea pigs, it was found that there is no allergenic effect that irritates the conjunctiva of the eyes and mucous membranes, the drugs do not cause degranulation of mast cells in rats beyond the permissible limits.
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