Herein, polyelectrolyte capsules containing anti-inflammatory drug indomethacin were formed using layer-by-layer strategy, which involves alternative deposition of oppositely charged polyelectrolytes, such as poly(acrylic acid) and poly(ethyleneimine) (or chitosan) onto the drug substrate. Two variants of encapsulation have been implemented: direct deposition of polyelectrolytes onto indomethacin dispersed in water at рН 6, and preliminary formation of soft matrix by solubilization of indomethacin in micellar solutions of cationic surfactants. The inclusion of indomethacin into nanosized polyelectrolyte capsules (hydrodynamic diameter of three-and five-layer capsules is 90-180 nm) has given a new form of indomethacin with the drug content of 0.20-0.25%, which exceeds its limiting solubility in water nearly by the factor of 40. The choice of materials and procedures used for preparation of capsules, as well as the number of polyelectrolyte layers that form shell has provided the control of the drug release from capsule and resulted in the design of pharmaceutical dosage forms with long-lasting effect.
Introduction. Behavioral methods on laboratory animals are recognized as the main approach in studying the activity of potential psychotropic drugs and allow us to evaluate the main effects of new compounds, increase the possibility of predicting a successful outcome of future clinical trials.Text. This review article analyzes the main modern behavioral models in rodents that are widely used for screening and studying the pharmacological activity of potential psychotropic drugs. The advantages and disadvantages of each test are highlighted and complexes of behavioral methods are demonstrated that most conclusively confirm the reproducibility of the results obtained in clinical trials. The description and evaluation of behavioral methods that characterize the state of anxiety, which are used to screen for new compounds with anxiolytic activity (tests «Open field», «Dark-light chamber», «Elevated plus maze», «Sequence of rays»). The range of tests used to study cognitive functions and memory processes is widely presented (various mazes – T-shaped, U-shaped, radial maze, Barnes maze, E-maze; water mazes – Morris, T-maze) with a description of a comparative analysis and necessary conditions that ensure the reliability of information. An important direction in the field of behavioral pharmacology is the modeling of violations of social behavior and the study of approaches for its correction – the main methods necessary for the study of social behavior are presented in the review by the tests «Three-chamber social test», «Open field» extended test, etc.Conclusion. Behavioral pharmacology dictates the need for close interaction between preclinical and clinical stages of research in the framework of the development of translational medicine and the development of approaches that provide evidence for the reproducibility of the results obtained in clinical trials. It is also necessary to improve existing and develop new behavioral models of mental disorders and to search for new ways to study the mechanisms of formation of behavioral disorders.
Relevance. Alzheimer's disease (AD) is a neurodegenerative disease, the drug therapy of which can only slow the progression of the disease, due to the variety of existing pathogenetic processes. A possible effective approach to the correction of symptoms can be the use of compounds with a complex mechanism of action — phosphorylacetohydrazides, capable of simultaneously acting on different parts of the pathological process, the most effective representative of which is the compound 2-chloroethoxy-para-N-dimethylaminophenyl phosphorylacetohydrazide (CAPAH). Target. To study the possibility of correcting cognitive and behavioral disorders in rats with a stereotaxic model of AD using the CAPAH compound, which affects different parts of the pathological process. Methods. 24 female Wistar rats were used in the work. AD was modeled in rats by stereotaxic bilateral injection of β-amyloid into the hippocampal region in a phosphate buffer solution, then on day 11, CAPACH (10 mg/kg) was administered intraperitoneally for 10 days, after which tests were performed using the ≪Elevated Plus Maze≫, ≪Open Field≫ and ≪Morris Water Maze≫. Statistical processing was carried out in the GraphPad Prism 8.0.1 program using one-way ANOVA analysis. Results. Multiple administration of CAPAH contributed to a decrease in the level of anxiety in the ≪Elevated Plus Maze≫ method, increasing the time spent in open arms by 4.6 times (p < 0.05) compared to rats without treatment. In the ≪Morris Water Maze≫ and ≪Open Field≫ tests, normalization of memory and motor activity processes was observed, respectively, the platform search time and the number of crossed lines did not differ from those of control animals. Conclusion. CAPAH reduces anxiety and memory processes in rats with a stereotaxic model of Alzheimer's disease caused by the introduction of β-amyloid into the hippocampus.
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