Pharmaceutical Formulations (United States)

INTRODUCTION. Currently, preclinical development of analgetic drugs is facing a large number of obstacles, mostly due to the limited validity of models and methods for pain assessment. To overcome the translational barrier in the development of analgetics, it is necessary to revise the existing methods for assessing pain sensitivity and develop new approaches that include both the study of reflexive and affective pain component. AIM. This study aimed to systematize a contemporary view of pain assessment methods in laboratory animals and develop applicability criteria in preclinical trials of new analgesics. DISCUSSION. The literature review included 75 references, among them original research and systematic reviews over the past 35 years. Pain is a multidimensional phenomenon that includes sensory, discriminatory and affective-motivational components. Standard nociceptive tests effectively evaluate sensory hypersensitivity, however, they are not sensitive enough when studying chronic pain based on an affective component. Less widely used non-reflexive methods (grimace scale, ultrasound vocalization, burrowing test) allow assessing the affective component; still, they have low specificity and are insufficiently validated for various pain models. A combined, polymodal approach enhances the objectivity, reproducibility, and translational predictivity of preclinical research towards the development of new analgetics. CONCLUSIONS. Nociceptive tests are a tool for assessing efficacy of anesthetics both at a primary screening and in preclinical trials. Standard nociceptive tests do not allow assessing affective pain component, thus development of new anesthetics necessitates an introduction of non-reflexive pain assessment in the preclinical trials. A combination of reflexive and non-reflexive pain assessment methods is a base for new research strategies in preclinical trials.

ObjectiveDespite the success of mRNA-LNPs vaccines against viruses, their potential against prokaryotic pathogens remains underexplored. We provide proof-of-concept for an mRNA-LNPs vaccine against Streptococcus mutans (S. mutans), the primary cause of dental caries.MethodsWe constructed LNPs-encapsulated mRNA vaccines encoding S. mutans PAc antigen alone or PAc fused with human IgG Fc domain, aiming to enhance mucosal immunity via Fc-FcRn interactions.ResultsA heterologous intramuscular prime-intranasal boost regimen induced robust, durable (>4 months) sIgA responses-2.6-fold higher with Fc fusion-that significantly inhibited S. mutans biofilm formation in vitro and reduced moderate dentinal caries by >60% in rats.ConclusionBacterial antigens can be effectively delivered via mRNA platforms, and Fc fusion is a promising strategy to enhance mucosal immunity against oral, respiratory, and other mucosal pathogens, consistent with Fc-FcRn-mediated mechanisms.

This review addresses the challenges of obtaining high-quality quantitative data in the optical imaging of membrane voltage and calcium dynamics. The paper provides a comprehensive overview and systematization of recent studies that analyze factors limiting signal fidelity and propose strategies to enhance data quality. The primary sources of signal degradation in biological optical imaging, with an emphasis on membrane voltage and calcium imaging, are systematically explored across four major indicator classes: voltage-sensitive dyes (VSDs), genetically encoded voltage indicators (GEVIs), calcium-sensitive dyes (CSDs), and genetically encoded calcium indicators (GECIs). Common mechanisms that compromise data quality are classified into three main categories: fundamental photon shot noise, device-related errors, and sample-related measurement errors. For each class of limitation, its physical or biological origin and characteristic manifestations are described, which are followed by an analysis of available mitigation strategies, including hardware optimization, choice of sensors, sample preparation and experimental design, post-processing and computational correction methods.

Introduction. The study of the qualitative and quantitative composition of plants and the identification of promising medicinal species is one of the most important tasks of modern pharmacognosy. Yellow loosestrife ( Lysimachia vulgaris L.) of the Primulaceae family is a perennial herbaceous plant. The main group of active substances in the herb of L. vulgaris are phenolic compounds. L. vulgaris is widely distributed in Russia, is known in traditional medicine, its biological activities have been examined in vitro and in vivo experiments. A search of scientific literature in the Russian segment did not reveal sufficient information on the quantitative content of biologically active substances. Aim. Development and validation of an analytical procedure for assessing the quantitative content of flavonoids in the herb of yellow loosestrife ( L. vulgaris ) in terms of rutin using spectrophotometry. Materials and methods. The object of the study was alcohol extracts from the aerial part of L. vulgaris , harvested during the flowering period in the Leningrad region. Quantitative determination was carried out by spectrophotometry. The proposed analytical procedure was validated in accordance with the requirements of the State Pharmacopoeia XV in terms of specificity, linearity, range, repeatability (intra-assay precision), precision and accuracy (trueness). Results and discussion. For the proposed analytical procedure, rutin was proposed as a standard sample. It was found that the maximum extraction of flavonoids from the herb of L. vulgaris is achieved by using a single extraction with 70 % ethyl alcohol for 30 min at a raw material : extractant ratio of 1 : 100 and a raw material grinding of 2–1 mm. A 1 % alcohol solution of aluminum chloride was proposed as a complexing agent, and the complexation conditions were selected (aliquot of aluminum chloride 1 % solution 2 ml, complexation time 30 min). The analytical procedure meets the requirements of the validation characteristics. According to the developed method, it was found that the amount of flavonoids in the herb of L. vulgaris , harvested in the Leningrad region, is 2,97 ± 0,05 % expressed in rutin. Conclusion. A method for the quantitative determination of the flavonoid content in the herb of yellow loosestrife ( L. vulgaris ) by spectrophotometry expressed in rutin has been developed and validated.

Introduction. The development of nanotechnology has led to the creation of complex drug delivery systems: liposomes, dendrimers, inorganic nanoparticles, cellular systems, and polymer nanoparticles. All these systems require an integrated approach to quality control. This review examines the key attributes of quality control, including physico-chemical and chemical analysis methods, as well as current regulatory requirements.Text. Drug delivery systems represent promising technologies aimed at improving the safety and effectiveness of pharmacotherapy. The variety of components and complexity of the structure create a number of difficulties in developing approaches to quality control of new media. Existing physical and physico-chemical analysis methods are actively used to determine the morphological characteristics of carriers, the physical characteristics of their membrane, and to confirm the structure of substrates and the final particle. However, the lack of a number of standardized approaches, in particular, for determining the zeta potential of a particle membrane, remains a serious challenge for a number of researchers and regulatory authorities.Conclusion. This review provides a systematic description of the approaches to quality control of delivery systems and their components that currently exist. The variety of media analysis methods makes it possible to fully assess the quality of media, but in the future it is necessary to harmonize existing international standards with Russian standards, which minimizes the risks associated with the use of media in the targeted delivery of medicines.

Sarcopenia is a syndrome characterized by a progressive and generalized loss of skeletal muscle mass, strength, and function, that exists in a primary and a secondary form. Secondary sarcopenia complicates chronic liver disease with a prevalence ranging from 30 to 100% depending on the nature of disease, its severity, and compensation status. The presence of sarcopenia limits normal daily activity, reduces work capacity, diminishes quality of life, may lead to disability, and increases all-cause mortality risk. Despite the evident medical and social burden of this condition, as of today, no agents for its treatment have proven to be both effective and safe. Significant attention of the scientific community has recently been drawn to molecules that improve and normalize the somatotropic axis function, which is found to be impaired in all types of sarcopenia. L-ornithine and its salts (L-aspartate, α-ketoglutarate) are not only capable of direct hepatoprotection and facilitation of ammonia clearance, but also modulate the somatotropic axis as well as have a number of pleiotropic metabolic effects. Preclinical studies have found L-ornithine to act as an indirect growth hormone secretagogue and enhance the activity of its main effector molecule, insulin-like growth factor 1. In clinical trials, course treatment with L-ornithine L-aspartate as an add-on to standard therapy increased the levels of circulating growth hormone, promoted arm muscle growth, improved handgrip strength and standing balance. L-ornithine α-ketoglutarate increased appetite and skeletal muscle gain in malnourished older adults, mitigated glutamine loss by skeletal muscle following major surgery, and improved quality of life in elderly convalescent subjects. The available data suggest potential effectiveness of L-ornithine formulations for the treatment of sarcopenia associated with chronic liver disease, and highlight this indication as an important field for future research.

Introduction. The parasitic fungus Climacodon septentrionalis (Fr.) P. Karst. has been little studied at the moment, but it is known to have antioxidant activity, which can be used in medicine. Only one medicinal product of fungal origin and a number of biologically active food supplements are registered in the Republic of Belarus. There is no information on the optimal methods and techniques for obtaining an extract from raw materials of fungal origin with the maximum possible content of phenolic compounds, as well as methods for their determination.Alm. To develop a method for determining the content of phenolic compounds in the fungus Climacodon septentrionalis.Materials and methods. The object of the study was the fruiting bodies of the northern Climacodon mushroom (C. septentrionalis), grown in natural conditions and stored at a temperature of –18 °C. The following reagents were used in the study: Folin – Chiocalteu reagent (LLC "Analit Komplekt", Russia), anhydrous sodium car-bonate (reagent grade, LLC "JSC REAKHIM", Russia), technical ethyl alcohol Extra-M 96.41 %, purified water; gallic acid standard (98 %, Acros Organics BVBA, Belgium); equipment: Explorer EX125D analytical scales, SOLAR PB 2201 spectrophotometer, Good-helper ES-10P10 electric hotplate, WB-12 water bath, AE-25 electric water dis-tiller.Results and discussion. The optimal method for extracting phenolic compounds from northern Climacodon is extraction with water at a temperature of 100 °С and a raw material : extractant ratio of 1 : 20 for 150 minutes once, draining the liquid into a separate closed container, leaving it to cool at room temperature, filtering through a cotton swab, bringing it to the original volume with water if necessary. When determining the amount of phenolic compounds in terms of gallic acid, it is recommended to use 0.10 ml of the extract, 0.45 ml of Folin – Ciocalteu reagent, stirring, adding 5.25 ml of 10 % sodium carbonate solution, stirring, reaction time – 16 minutes, measuring the optical density at a wavelength of 760 nm.Conclusion. The concentration of the sum of phenolic compounds in terms of gallic acid in the obtained extract is 202 ± 5 μg/ml or the mass fraction when converted to the wet weight of C. septentrionalis is 0.41 ± 0.01 %.

Introduction. The search for effective approaches to the treatment of anxiety disorders, in particular, the development and study of drugs with anxiolytic action, is currently one of the most urgent tasks of neurobiological research. The study of behavioral changes in Danio rerio after exposure to a new group of substances – chromone-containing allylmorpholines – revealed their ability to exert dose-dependent sedation, and one of the compounds of the series – (E)-4-[3-(6-chloro-4-oxo-4H-chromene-3-yl)-4-cyclohexylallyl]morpholin-4-ium chloride (33a), in addition to sedative, also exerted anxiolytic action at low concentrations. Danio rerio is an evolutionary species much older than humans, and therefore the structural and functional differences between the receptors may be quite significant, making it necessary to evaluate the pharmacological profile of the new compounds in a translational model with more genetic similarities to humans, for example, in rodents.Aim. The present study investigated the effects of 33a on anxiety behavior, cognitive functions, and grip strength of BALB/c mice after acute and chronic administration.Materials and methods. Pharmacological activity was assessed using Open Field, Elevated Plus Maze, Light/Dark Box, T-maze, Marble burying, Tail suspension and Grip strength tests in BALB/c mice after acute administration of 33a at doses 1, 10 and 50 mg/kg, and two-week administration at doses 1 and 10 mg/kg.Results and discussion. With acute administration, 33a at a dose of 50 mg/kg reduced the number of buried marbles, and at a dose of 10 mg/kg with chronic administration, it reduced the latency time of the first transition from a dark chamber to a white one in the Light/Dark Box test, which can be considered as manifestations of anxiolytic action. However, in the classical Elevated Plus Maze test, there were no statistically significant effects indicating the anxiolytic effect of 33a. The study did not reveal any negative effect of the studied substance on spatial memory and grip strength of mice, which may indicate the absence of its neurotoxic effect.Conclusion. The results obtained confirmed the ability of compound 33a to exert dose-dependent inhibition of locomotor activity, however, this effect was not demonstrated in all tests. Further expansion of the range of used behavioral tests, as well as the use of experimental models may allow to reveal the specific activity of compound 33a, as well as other chromone-containing derivatives of allylmorpholine.