Increase of solubility and transmembrane permeability of niclosamide from its mechanochemically synthesized solid dispersions

More than 4.5 billion people worldwide are affected by parasitic diseases, with helminth infections accounting for 99% of the total number. Niclosamide (NS) is a weakly acidic active pharmaceutical ingredient (API) used to treat helminth infections. However, the pharmaceutical use of pure niclosamide is limited by its low bioavailability due to its poor aqueous solubility. The aim of this work is a mechanochemical preparation of niclosamide solid dispersions with increased solubility. Due to the pH dependence of NS water solubility and possible complexes formation, NS solid dispersions (SD) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and alkalizing agents, such as calcium carbonate (CaCO3) and N-methyl-D-glucamine (MG) are mechanochemically prepared in this study. The physical properties of NS SD in solid state are characterized by differential scanning calorimetry, X-ray diffraction, FT-IR spectroscopy, and scanning electron microscopy studies. The characteristics of the water solutions formed from the obtained SDs are analyzed by HPLC. It is shown that the solubility increases for all studied compositions. These phenomena are obliged by complexation with HP-β-CD, which was shown by 1H-NMR methods, and enhanced ionization in the cases of using calcium carbonate and MG. Results of the parallel artificial membrane permeability assay (PAMPA) have shown that mechanochemically obtained NS/MG SD (1/1 mass ratio, 8 h milling) significantly enhances permeation of NS across an artificial membrane. Thus, the obtained compositions are a promising basis for the development of NS-based preparations for oral administration, with reduced dose and high pharmacological effect

The role of timely diagnosis and treatment of ENT pathologies in maintaining the physical health of patients

The presented work analyzes the need for specialized diagnostic procedures in order to identify the presence of certain ENT pathologies in the patient, since their untimely detection and, as a result, treatment directly affect the physical health of a person as a whole. It is noted that a decrease in patients’ attention to their health, as well as an untimely appeal to a specialized specialist for advice, can lead to the development of serious complications and even surgical intervention. The authors investigate in detail the features of common ENT diseases, possible symptoms, as well as complications that arise in the case of a chronic course of such diseases. At the same time, considerable emphasis is placed on the importance of the prevention of ENT diseases, among these measures are proper nutrition, a healthy lifestyle, regular medical examinations and following recommendations for the care of ENT organs. The paper emphasizes that timely diagnosis and treatment of ENT pathologies should be identified as key factors that ensure the necessary level of physical health of patients, for this reason, it is necessary to consult a specialist at the first symptoms of the disease. Investigating the methods of diagnosis of ENT diseases, the authors of the work also pay attention to the consideration of methods of treatment of ENT diseases, especially noting conservative therapy, since at the early stages of the development of the disease it allows to restore the patient’s health without resorting to surgical intervention. Based on the results of consideration of the problem, it should be concluded that timely referral to a specialist, diagnosis and treatment of ENT diseases are necessary conditions for maintaining and improving the physical health of patients and their quality of life

The efficacy of complex solid dispersions of anthelmintics against experimental trichinellosis

The purpose of the research is to study the influence of various technological factors on obtaining of complex solid dispersions of anthelmintics with polyvinylpyrrolidone and licorice extract on anthelmintic efficacy in experimental trichinellosis of white mice.Materials and methods. The study of the nematodocidal activity of complex solid dispersions samples based on fenbendazole (FBZ), fenasal (FNS) and praziquantel (PZQ) with polyvinylpyrrolidone (PVP) and licorice extract (LE) obtained by mechanochemical technology at different ratios of components and different exposure times was carried out on 130 white mice experimentally infected with Trichinella spiralis in two experiments. On the 3rd day after infection, the animals were divided into experimental groups of 10 animals each. Samples of various complex solid dispersions of anthelmintics were administered intragastrically to the mice of the experimental groups at a dose of 2 mg/kg according to the active substance. FBZ substance was used as the basic drug at a dose of 2 mg/kg according to the active substance. Animals of the control groups did not receive the drugs. The animals were killed by decapitation on the 4th day after experimental drug samples administration, and the activity of the drugs was counted according to the results of helminthological necropsy of the intestine, the efficacy was calculated by the type of control test.Results and discussion. The efficacy of complex solid dispersions of FBZ and FNS with PVP polymer was higher in comparison with the activity of complexes with LE at the same duration of mechanochemical treatment in a roller mill. The FBZ activity decreased from 67.05 to 37.77% with a decrease in the duration of mechanochemical treatment from 24 h to 5 h and the efficacy of the FBZ : FNS complex with LE turned out to be almost at the level of the basic drug when treated for 1 h. The use of mechanochemical technology for obtaining of a solid dispersion of FBZ : FNS with PVP for targeted delivery makes it possible to increase the anthelmintic efficacy by 2.7 times compared with the activity of the FBZ substance, and with LE by 2.2 times. It was noted that complex solid dispersions of PBZ with PZQ have lower biological activity in comparison with compositions of FBZ with FNS

Эффективность комплексных твердых дисперсий антигельминтиков при экспериментальном трихинеллезе

The purpose of the research is to study the influence of various technological factors on obtaining of complex solid dispersions of anthelmintics with polyvinylpyrrolidone and licorice extract on anthelmintic efficacy in experimental trichinellosis of white mice.Materials and methods. The study of the nematodocidal activity of complex solid dispersions samples based on fenbendazole (FBZ), fenasal (FNS) and praziquantel (PZQ) with polyvinylpyrrolidone (PVP) and licorice extract (LE) obtained by mechanochemical technology at different ratios of components and different exposure times was carried out on 130 white mice experimentally infected with Trichinella spiralis in two experiments. On the 3rd day after infection, the animals were divided into experimental groups of 10 animals each. Samples of various complex solid dispersions of anthelmintics were administered intragastrically to the mice of the experimental groups at a dose of 2 mg/kg according to the active substance. FBZ substance was used as the basic drug at a dose of 2 mg/kg according to the active substance. Animals of the control groups did not receive the drugs. The animals were killed by decapitation on the 4th day after experimental drug samples administration, and the activity of the drugs was counted according to the results of helminthological necropsy of the intestine, the efficacy was calculated by the type of control test.Results and discussion. The efficacy of complex solid dispersions of FBZ and FNS with PVP polymer was higher in comparison with the activity of complexes with LE at the same duration of mechanochemical treatment in a roller mill. The FBZ activity decreased from 67.05 to 37.77% with a decrease in the duration of mechanochemical treatment from 24 h to 5 h and the efficacy of the FBZ : FNS complex with LE turned out to be almost at the level of the basic drug when treated for 1 h. The use of mechanochemical technology for obtaining of a solid dispersion of FBZ : FNS with PVP for targeted delivery makes it possible to increase the anthelmintic efficacy by 2.7 times compared with the activity of the FBZ substance, and with LE by 2.2 times. It was noted that complex solid dispersions of PBZ with PZQ have lower biological activity in comparison with compositions of FBZ with FNS.Цель исследований – изучить влияние различных факторов технологии получения комплексных твердых дисперсий антигельминтиков с поливинилпирролидоном и экстрактом солодки на эффективность при экспериментальном трихинеллезе белых мышей.Материалы и методы. Изучение нематодоцидной активности образцов комплексных твердых дисперсий на основе фенбендазола (ФБЗ), фенасала (ФНС) и празиквантела (ПЗК) с поливинилпирролидоном (ПВП) и экстрактом солодки (ЭС), полученных по механохимической технологии при разном соотношении компонентов и различной продолжительности механообработки проводили на 130 белых мышах, экспериментально зараженных Trichinella spiralis в двух опытах. На третьи сутки после заражения животных разделили на группы по 10 голов в каждой. Мышам опытных групп вводили в желудок образцы различных комплексных твердых дисперсий антигельминтиков в дозе 2 мг/кг по ДВ. В качестве базового препарата использовали субстанцию ФБЗ в дозе 2 мг/кг по ДВ. Животные контрольных групп препараты не получали. На четвертые сутки после введения опытных образцов животных убивали декапитацией и активность препаратов учитывали по результатам гельминтологического вскрытия кишечника; эффективность рассчитывали по типу «контрольный тест».Результаты и обсуждение. Эффективность комплексных твердых дисперсий ФБЗ и ФНС с полимером ПВП была выше по сравнению с активностью комплексов с ЭС при одинаковой продолжительности механохимической обработки в валковой мельнице. С уменьшением продолжительности механохимической обработки с 24 ч до 5 ч активность ФБЗ снижалась с 67,05 до 37,77%, а при обработке в течение 1 ч эффективность комплекса ФБЗ : ФНС с ЭС оказалась практически на уровне базового препарата. Использование механохимической технологии получения твердой дисперсии ФБЗ : ФНС с ПВП позволяет повысить антигельминтную эффективность в 2,7 раза по сравнению с активностью субстанции ФБЗ, а с ЭС – в 2,2 раза. Отмечено, что комплексные твердые дисперсии ФБЗ с ПЗК обладают меньшей биологической активностью в сравнении с композициями ФБЗ с ФНС

Микробная доступность органического вещества в донных отложениях арктических озер: лабораторный инкубационный эксперимент

The water ecosystems of the Arctic region are most vulnerable to modern climatic changes since the global biogeochemical processes mostly occur on the territories of the permafrost zone. Aquatic ecosystems show a high degree of sensitivity to climatic changes; both in these and in other ecosystems, the biogeochemical processes are intense. These water bodies are located in the permafrost zone, which is vulnerable to temperature increases. The paper gives new insights into the fundamental research question of how fast the organic matter of thawing permafrost can be converted to greenhouse gases emitted into the atmosphere (CO2, CH4). We aimed to assess the microbial response and the associated release of CO2 and CH4 from the Arctic lakes in response to temperature increase. We investigated lakes located in the Lena River delta in the Samoylov Island, Russia, at 72° 22′ N, 126° 28′ E. Bottom sediments from three thermokarst and three oxbow lakes were anaerobically incubated in the laboratory at two temperature regimes (at 4 °C and at 25 °C). All the oxbow lakes have shown similar dynamics of methane emission both at low temperatures (4 °C) and at high temperatures (25 °C). The shift of carbon isotopic composition in methane has indicated that methane is emitted in all the oxbow lakes with a similar composition of microbial communities. In the thermokarst lakes, the emission of methane in the sediments proceeded differently at low and at high temperatures. These results have indicated a dissimilar composition of methanogenic / methanotrophic populations in the thermokarst and oxbow lakes. In both cases, the temperature increase caused a growth in methane emission from the sediments of the Arctic lakes. The thermokarst lakes will make a greater contribution to methane emission than the oxbow lakes. Thus, it is believed that the emission of methane from the thermokarst lakes will rise from 6 to 46 times due to ambient temperature increase. Methane emission from the oxbow lakes will grow from 1.8 to 7.6 times. Our results suggest that with the global warming both thermokarst and oxbow lakes could become a great source of methane emission into the atmosphere.В работе представлены новые данные, касающиеся фундаментального вопроса о скорости преобразования органического вещества, захороненного в вечной мерзлоте, в парниковые газы (CO2, CH4 ). Основной задачей являлось определение микробной реакции в ответ на повышение температуры и связанной с этим процессом эмиссии CO2 и CH4 из арктических озер. В работе изучались озера, расположенные в дельте реки Лены на острове Самойловский, Россия (72° 22′ с. ш., 126° 28′ в. д.). Были проведены лабораторные анаэробные инкубационные эксперименты донных отложений из трех термокарстовых и трех старичных озер при двух температурных режимах (4 °C и 25 °C). Осадки старичных озер показали сходную динамику эмиссии метана, как при низких (4 °C), так и при высоких температурах (25 °C). В термокарстовых озерах, в экспериментах при низких и высоких температурах, эмиссия метана в отложениях протекала с использованием несхожих метаболических путей. Изотопное смещение углерода в метане указывало на различающийся состав метаногенных/метанотрофных популяций в термокарстовых и старичных озерах. В обоих случаях повышение температуры приводило к увеличению высвобождения метана из донных отложений арктических озер. В сравнении со старичными озерами, термокарстовые озера внесут больший вклад в эмиссию метана. Так, эмиссия метана из термокарстовых озер предположительно увеличится от 6 до 46 раз за счет повышения температуры окружающей среды, а из старичных озер — от 1,8 до 7,6 раз. Согласно результатам данного исследования, в условиях глобального потепления климата и термокарстовые и старичные озера могут стать значимыми источниками поступления метана в атмосферу Земли

Electrochemically synthesized polymers in molecular imprinting for chemical sensing

This critical review describes a class of polymers prepared by electrochemical polymerization that employs the concept of molecular imprinting for chemical sensing. The principal focus is on both conducting and nonconducting polymers prepared by electropolymerization of electroactive functional monomers, such as pristine and derivatized pyrrole, aminophenylboronic acid, thiophene, porphyrin, aniline, phenylenediamine, phenol, and thiophenol. A critical evaluation of the literature on electrosynthesized molecularly imprinted polymers (MIPs) applied as recognition elements of chemical sensors is presented. The aim of this review is to highlight recent achievements in analytical applications of these MIPs, including present strategies of determination of different analytes as well as identification and solutions for problems encountered

The role of timely diagnosis and treatment of ENT pathologies in maintaining the physical health of patients

The presented work analyzes the need for specialized diagnostic procedures in order to identify the presence of certain ENT pathologies in the patient, since their untimely detection and, as a result, treatment directly affect the physical health of a person as a whole. It is noted that a decrease in patients’ attention to their health, as well as an untimely appeal to a specialized specialist for advice, can lead to the development of serious complications and even surgical intervention. The authors investigate in detail the features of common ENT diseases, possible symptoms, as well as complications that arise in the case of a chronic course of such diseases. At the same time, considerable emphasis is placed on the importance of the prevention of ENT diseases, among these measures are proper nutrition, a healthy lifestyle, regular medical examinations and following recommendations for the care of ENT organs. The paper emphasizes that timely diagnosis and treatment of ENT pathologies should be identified as key factors that ensure the necessary level of physical health of patients, for this reason, it is necessary to consult a specialist at the first symptoms of the disease. Investigating the methods of diagnosis of ENT diseases, the authors of the work also pay attention to the consideration of methods of treatment of ENT diseases, especially noting conservative therapy, since at the early stages of the development of the disease it allows to restore the patient’s health without resorting to surgical intervention. Based on the results of consideration of the problem, it should be concluded that timely referral to a specialist, diagnosis and treatment of ENT diseases are necessary conditions for maintaining and improving the physical health of patients and their quality of life