Рharmaceutical-technological Study of Adsorbed Liquid Plant Extract of Antimicrobial Activity
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Cited by 4 publications
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Main Aspects of Pharmaceutical Development of In situ Immunobiological Drugs for Intranasal Administration
Introduction: The review presents the latest developments in the area of intranasal in situ delivery systems of immunobiological drugs (IBDs). Interest in intranasal administration for IBDs has increased significantly due to the COVID-19 pandemic. However, not only intranasal delivery of vaccines is developing, but also bacteriophages, interferons, etc. In situ systems that make a selective phase transition can be a modern solution to intranasal delivery problems caused by mucociliary clearance. In addition, smart-polymers used as the main excipients in in situ systems can be used as specific adjuvants. Methods: A scientific search was conducted on the PubMed database of medical publications for the period from 2000 to 2022, using the keywords "intranasal in situ vaccine"; "intranasal in situ immunization". There were analyzed in detail more than 70 scientific studies on intranasal in situ delivery of IBDs. Results and Conclusions: Despite the large number of new studies, the potential of possibilities of intranasal in situ systems is not being realized. Based on the results of the literature review an algorithm was created for the development of in situ systems for intranasal delivery of IBDs. Such algorithms and the methods of study design organization described in the review will help to facilitate the R&D process and bring the drug to commercial market, which will help to improve the quality of medical care.
Main Aspects of Pharmaceutical Development of In situ Immunobiological Drugs for Intranasal Administration
Introduction: The review presents the latest developments in the area of intranasal in situ delivery systems of immunobiological drugs (IBDs). Interest in intranasal administration for IBDs has increased significantly due to the COVID-19 pandemic. However, not only intranasal delivery of vaccines is developing, but also bacteriophages, interferons, etc. In situ systems that make a selective phase transition can be a modern solution to intranasal delivery problems caused by mucociliary clearance. In addition, smart-polymers used as the main excipients in in situ systems can be used as specific adjuvants. Methods: A scientific search was conducted on the PubMed database of medical publications for the period from 2000 to 2022, using the keywords "intranasal in situ vaccine"; "intranasal in situ immunization". There were analyzed in detail more than 70 scientific studies on intranasal in situ delivery of IBDs. Results and Conclusions: Despite the large number of new studies, the potential of possibilities of intranasal in situ systems is not being realized. Based on the results of the literature review an algorithm was created for the development of in situ systems for intranasal delivery of IBDs. Such algorithms and the methods of study design organization described in the review will help to facilitate the R&D process and bring the drug to commercial market, which will help to improve the quality of medical care.
Antimicrobial and Antioxidant Activity Screening of Mushrooms Growing in the Leningrad Region
Introduction. The emergence of new strains of microorganisms that are multidrug resistant (MDR) in relation to the antimicrobial drugs used is one of the pressing problems of modern medicine. To prevent an increase in MDR-related deaths, the search for new antibiotics and their introduction into medical practice must be continuously ongoing. Infectious diseases are also accompanied by cell damage and the development of free radical oxidation processes, therefore the search for new antioxidants is also an important task. Considering the powerful biosynthetic potential of basidiomycetes, this group of fungi has every prospect of becoming a new source of biologically active substances in general, as well as antibiotics and antioxidants in particular. Cap mushrooms, represented mainly by basidiomycetes, number about 14,000 species and are an accessible source of raw materials for the search for promising antimicrobial compounds and antioxidants.Aim. Study of the antioxidant and antimicrobial activity of total extracts obtained from cap mushrooms against Escherichia coli, Staphylococcus aureus and Candida albicans and assessment of the suitability of cap mushrooms as a natural source of substances with antimicrobial and antioxidant activity.Materials and methods. The antifungal and antibacterial activity of the extracts was determined by the micromethod of two-fold serial dilutions in a liquid nutrient medium in 96-well plates in duplicate. The study of this type of biological activity was carried out against reference (type) strains Staphylococcus aureus ATCC 6538-P, Escherichia coli ATCC 25922, Candida albicans NCTC 885-653. To study antioxidant activity using DPPH, we used alcoholic extracts from the fruiting bodies of mushrooms obtained by maceration with 96 % ethanol at a ratio of raw materials to extractant of 1 to 8 for 24 hours, an aqueous solution of ascorbic acid (vitamin C) and an ethanol solution of Trolox.Result and discussion. In relation to S. aureus, a representative of gram-positive flora, the studied extracts of cap mushrooms showed low activity, on average about 2500 or 5000 μg/ml. In relation to E. coli, a representative of gram-negative flora, 8 % of the studied cap mushroom extracts showed an average activity of about 1250 μg/ml. The largest number of cap mushroom extracts – 19% of all studied species – showed activity against the yeast micromycete C. albicans. The highest activity against C. albicans was observed in extracts of the mushrooms Cantharellula umbonata with an MIC of 625 μg/ml, Cortinarius olivaceofuscus with an MIC of 625 μg/ml, and Hypomyces chrysospermus with an MIC of 312 μg/ml. During screening of antioxidant activity, the studied extracts were divided into three groups: with high (more than 50 % PPR), medium (from 15 to 50 % PPR) and low (less than 15 %) antioxidant activity. It was shown that the sum of phenolic compounds significantly correlates with the level of antioxidant activity in all three groups, but in the groups with medium and low antioxidant activity there are also other non-phenolic groups of compounds that make a significant contribution to the total antioxidant activity.Conclusion. Cap mushrooms are a promising source of biologically active substances with antifungal and antioxidant activity.
Identification of luteolin-7-glucoside metabolites after oral administration and development of a method for their quantitative analysis
Introduction. The development and registration of antiviral drugs is an urgent task. Flavonoids, in particular, luteolin-7-glycoside (cinaroside, luteolin-7-O-glycoside) demonstrate high broad-spectrum antiviral activity in vitro, and the industrial regulations for the production of luteolin-7-glycoside from the leaves of holly willow have already been developed at the VILAR. One of the problems with the introduction of flavonoids into medical practice is their low bioavailability and intensive biotransformation. Existing publications provide contradictory data on the pharmacokinetics of luteolin-7-glycoside, and therefore our own research was conducted.Aim. To develop a methodology for the quantitative analysis of luteolin-7-glycoside and its metabolites in blood plasma and to test it on laboratory animals.Materials and methods. Animal experiments were carried out in accordance with the requirements of the "Guidelines for conducting preclinical studies of medicines". To develop a method of analysis and further clarify the time intervals of blood sampling, time points were analyzed: 30, 60 minutes, 2, 4, 8, 24 hours after administration of the test substance. Tubes with citrate blood of laboratory animals were centrifuged at 2000 rpm for 10 minutes. The plasma was placed in an Eppendorf-type test tube, frozen and stored at –20 °C until chromatographic analysis was performed. Blood plasma sample preparation was carried out by precipitation with methyl alcohol, the supernatant was chromatographically separated on a column Luna® 5 µm C18 column 100 Å 250 × 4.6 mm in a gradient mode in a water-acetonitrile system and a modifier – 0.2 % formic acid. The metabolites were identified by high-performance liquid chromatography with mass spectrometric detection. To do this, the spectral characteristics of the peaks that appeared on the chromatograms of blood plasma samples after oral administration of luteolin-7-glycoside were interpreted. The concentration of the analyzed substances was assessed by the internal standard method, which was rutin. To determine the concentration of luteolin, a standardized luteolin substance was used as a standard sample, the concentration of the remaining metabolites was estimated in terms of luteolin.Results and discussion. It was found that after oral administration of luteolin-7-glycoside in starch paste to laboratory animals, native luteolin-7-glycoside was not detected in blood plasma. The main metabolites were luteolin-diglucuronide and luteolin-glucuronide, their maximum plasma concentrations are about three times higher than luteolin and methyllyuteolin-diglucuronide. The results are compared with data from other studies.Conclusion. The absence of native luteolin-7-glycoside in blood plasma after oral administration makes it necessary to seriously reconsider the relevance of the conclusions obtained during studies of its activity in vitro. However, in the presence of antiviral activity in vivo, there is an urgent need for further research to establish the real mechanisms of action of this medicinal substance.
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