Ресурсный центр «Магнитно-резонансные методы исследования»

M. Shevtsov, B. Nikolaev, Y. Marchenko, L. Yakovleva, N.V. Skvorzov, A. Mazur, P. Tolstoy, V. Ryzhov, G. Multhoff

“Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs)”

Int. J. Nanomedicine, 2018, 13, 1471-1482
DOI: 10.2147/IJN.S152461

Glioblastoma is the most devastating primary brain tumor of the central nervous system in adults. Magnetic nanocarriers may help not only for a targeted delivery of chemotherapeutic agents into the tumor site but also provide contrast enhancing properties for diagnostics using magnetic resonance imaging (MRI)

M. Promzeleva, T.V. Volkova, A.N. Proshin, O.I. Siluykov, A. Mazur, P.M. Tolstoy, S.P. Ivanov, F. Kamilov, I.V. Terekhova

“Improved biopharmaceutical properties of oral formulations of 1,2,4-thiadiazole derivative with cyclodextrins: in vitro and in vivo evaluation”

ACS Biomater. Sci. Eng, 2018, 4(2), 491-501
DOI: 10.1021/acsbiomaterials.7b00887

The synthesized 1,2,4-thiadiazole derivative displaying biological activity has low aqueous solubility and dissolution rate. Novel oral formulations of thiadiazole with β- and hydroxypropyl-β-cyclodextrins were obtained by grinding and freeze-drying methods with the purpose to improve the aqueous solubility. Complex formation of 1,2,4-thiadiazole derivative with cyclodextrins was confirmed by means of solid-state 13C MAS CP/TOSS NMR. Solubility, dissolution rate and permeability of the solid inclusion complexes were evaluated in different biorelevant media (SGF, FaSSGF, FaSSIF) simulating the conditions in the gastrointestinal tract. It was demonstrated that the content of biorelevant media affects the properties of the inclusion complexes. In particular, solubilizing effect of cyclodextrins became less pronounced when the micelles of taurocholic acid and lecithin are formed in the dissolution media. The inclusion of thiadiazole into cyclodextrin cavity is in competition with its partitioning into the micelles and this should be taken into account when the in vivo behavior is predicted. The results of in vitro and in vivo experiments were found to be in agreement and showed the highest solubility, dissolution rate and bioavailability of the freeze-dried complexes of thiadiazole with hydroxypropyl-β-cyclodextrin. These complexes can be proposed as more effective dosage forms for oral administration.

С 1 по 6 апреля прошла очередная 15 школа-конференция Spinus 2018. Приятно отметить, что многие пользователи рц МРМИ и, собственно, сами сотрудники приняли активное участие в этой конференции. Среди сотрудников участвовали: М.А. Вовк, С.И. Сухаржеский, П.М. Толстой, А.С. Мазур. Среди пользователей рц МРМИ: В.И. Чижик, И.С. Гиба, А.В. Иевлев, М. Костин, Д.А. Лузик, Д.А. Маркелов, В.В. Малоярова, А.В. Пенькова, С.О. Рабдано, В. Барнаускайте.

Мы надеемся, что в будущем интерес к конференции Spinus среди пользователей рц МРМИ будет возрастать, и молодые исследователи будут активно апробировать свои работы и представлять их широкому кругу коллег.

В ходе стажировки 18-26 ноября Мазур А.С. успешно освоил методы проведения низкотемпературных измерений спектров ЯМР в широком частотном диапазоне (250 — 500 МГц) на оборудовании представленном в Отделении низкотемпературной физики факультета математики и физики Карлова университета в Праге.

M. Brusnikina, O. Silyukov, M. Chislov, T. Volkova, A. Proshin, A. Mazur, P. Tolstoy, I. Terekhova

“Effect of cyclodextrin complexation on solubility of novel anti-Alzheimer 1,2,4-thiadiazole derivative”

J Therm Anal Calorim, 2017
DOI: 10.1007/s10973-017-6252-1

New 1,2,4-thiadiazole derivative displaying neuroprotective potential and high activity in the treatment of Alzheimer’s disease has been synthesized. The objective of this study was to improve the aqueous solubility of this drug-like compound by means of complex formation with native and hydroxypropylated β-cyclodextrins. To this end, aqueous solubility of 1,2,4-thiadiazole derivative was investigated in the presence of β-cyclodextrins. It was shown that the phase solubility diagrams are of Bs type demonstrating the initial increase in thiadiazole solubility in solutions of cyclodextrins (concentration up to 0.01 mol kg−1) followed by a solubility decrease due to the precipitation of the complexes formed. In comparison with β-cyclodextrin, hydroxypropyl-β-cyclodextrin displays more pronounced solubilizing action since it forms more stable complexes with thiadiazole. Solid complexes of 1,2,4-thiadiazole derivative with β-cyclodextrins were prepared by grinding and freeze-drying methods. DSC, TG, hot-stage microscopy, solid-state 13C MAS CP/TOSS NMR, powder X-ray diffractometry and FTIR spectroscopy were used to prove the existence of complexes in the solid state. Solubility of the obtained formulations was also examined. It was found that complexes of thiadiazole with hydroxypropyl-β-cyclodextrin exhibited higher solubility in phosphate buffer (pH 7.4) compared with pure thiadiazole and its complexes with β-cyclodextrin.

P. Mäki-Arvela, J. Zhu, N. Kumar, K. Eränen, A. Aho, J. Linden, J. Salonen, M. Peurla, A. Mazur, V. Matveev, D. Y. Murzin

“Solvent-free “green” amidation of stearic acid for synthesis of biologically active alkylamides over iron supported heterogeneous catalysts”

Applied Catalysis: A, 2017, 542, 350-358
DOI: 10.1016/j.apcata.2017.06.006

Stearoyl ethanolamine was synthesized by amidation of stearic acid with ethanolamine in solventless conditions. Iron containing heterogeneous catalysts supported on SiO2, Al2O3, Beta (BEA), ZSM-12 (MTW) and Ferrierite (FER) were used in this work. Sn-modified Ferrierite and H-Ferrierite were also studied for comparison. Fe-modified catalysts synthesized using solid state ion-exchange and evaporation impregnation methods, were thoroughly characterized with X-ray powder diffraction, scanning electron microscope, FTIR with pyridine, nitrogen adsorption, energy dispersive X-ray microanalysis and Mössbauer spectroscopy. The highest conversion was obtained with Fe-H-FER-20 at 140 °C in 1 h giving 61% conversion and 98% selectivity towards the desired amide. The catalytic performance in terms of turnover frequency per mole of iron was achieved with the catalyst exhibiting the largest amount of Fe3+ species, optimum acidity and a relatively low Brønsted to Lewis acid site ratio.

Т. Н. Тарасенко, З. Ф. Кравченко, В. В. Бурховецкий, А. С. Мазур, В. И. Каменев, А. И. Линник

“Синтез, микроструктура, сложный характер магнитного состояния слаболегированного висмутом манганита лантана”

Известия РАН. Серия физическая, 2017, том 81, № 3, с. 344–348
DOI:10.7868/S036767651703036X

Проведены структурные, магнитные и резонансные исследования манганитов BixLa1 – xMnO3. Золь–гель-методом получены нанопорошки слаболегированных составов (x = 0.0–0.1) с размером частиц ≤40 нм. При спекании в одинаковых условиях средний размер гранул резко растет с ростом содержания Bi. Спектры ЯМР манганитов твердофазного синтеза 55Mn отвечают условию быстрого обмена Mn4+ ↔ Mn3+. Измерение магнитной восприимчивости обнаружило неоднородность магнитного состояния системы BixLa1 – xMnO3.

V.V. Tomaev, A.S. Mazur, A.S. Grevtsev

“A study of the process of thermal oxidation of lead selenide by the NMR and XRD methods”

Glass Phys. Chem., 2017, 43, 70–74
DOI:10.1134/S1087659617010163

Studies of the process of oxidation of powder samples of lead selenide in a dry air atmosphere have been performed. As shown by the methods of X-ray diffraction and scanning electron microscopy, the process of thermal treatment of samples resulted in the formation of the PbSeO3 phase, aside from the initial PbSe phase. Studies by the method of nuclear magnetic response (NMR) allowed revealing the dynamics of changes in the spectrum under the changed thermal treatment conditions.