Center for Magnetic Resonance

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.

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.

A.V. Artem’ev, E.P. Doronina, M.I. Rakhmanova, A.O. Sutyrina, I.Yu. Bagryanskaya, P.M. Tolstoy, A.L. Gushchin, A.S. Mazur, N.K. Gusarova, B.A. Trofimov

“Luminescent CuI thiocyanate complexes based on tris(2-pyridyl)phosphine and its oxide: from mono-, di- and trinuclear species to coordination polymer”

New J. Chem., 2016, 40, 10028-10040
DOI:10.1039/C6NJ02087A

Tris(2-pyridyl)phosphine oxide reacts with CuSCN to form a variety of luminescent complexes, depending on the specified metal-to-ligand ratio and the solvent used, viz. mononuclear [Cu(N,N′,N′′-Py3P=O)(NCS)], dinuclear (N,N′-Py3P=O)Cu(SCN NCS)Cu[(N,N′-Py3P=O)], their co-crystal (2 : 1, correspondingly) and trinuclear {Cu(NCS)[SCNCu(N,N′,N′′-Py3P=O)]2}. In the solid state, these complexes feature red-orange emission upon UV photoexcitation. The reaction of tris(2-pyridyl)phosphine with CuSCN quantitatively produces an almost insoluble coordination polymer, [Cu(Py3P)NCS]n, which exhibits bright green emission. The synthesized compounds are the first members of the hitherto unknown family of Cu(I) thiocyanate complexes supported by tripodal ligands.

A.A. Osipov, V.E. Eremyashev, A.S. Mazur, P.M. Tolstoi, L.M. Osipova

“Coordination State of Aluminum and Boron in Barium Aluminoborate Glass”

Glass Physics and Chemistry, 2016, 42(3), 230–237
DOI:10.1134/S1087659616030111

This paper considers the coordination state of boron and aluminum ions in barium aluminoborate glass with a constant ratio of BaO : B₂O₃ = 0.5 and a variable ratio of Al₂O₃ : BaO = 0–3. The dependence of the concentrations of boron and aluminum atoms with a variable coordination number on the Al₂O₃ content was estimated by IR, ¹¹B and ²⁷Al NMR spectroscopy. The nonlinear nature of the obtained dependences was attributed to variations in the aluminum oxide properties. At a content of less than 30 mol % Al₂O₃ serves primarily as a network former, while an increase in the Al₂O₃ concentration results in its higher modifying role in the studied glass.