Delivery systems

Системы доставки − это пролонгированные лекарственные формы, в которых лекарственное вещество растворено или диспергировано в массе носителя, защищено оболочкой или интегрировано в виде. Используются для направленного транспорта лекарственных соединений в заданную область организма, органа или клетки. В качестве носителя и оболочки чаще всего применяют биосовместимые полимеры, нативные и модифицированные циклодекстрины.

Development of novel pharmaceutical forms of drug compounds and materials for biomedical use

Head of the department: 
Perlovich German Leonidovich
Scope of research: 

Transition to personalized medicine, high-tech health care and health protection technologies, including those based on rational administration of drug compounds, is impossible without developing materials for medical use and new generation drugs. The research community and pharmaceutical industry have recently paid a lot of attention to developing bioavailable preparations. A literature analysis shows that about 40% of commercial substances and 80% of compounds being developed now by pharmaceutical companies are poorly soluble in aqueous media. This fact considerably lowers the therapeutic effectiveness of drug compounds and causes side effects. The solubility and permeability parameters can be improved by applying conceptually new approaches based on fine-tuning of physicochemical properties of multicomponent molecular crystals (cocrystals). The economic effect of such pharmaceutical systems is comparable with launching a new drug on the market. Besides, the innovative technologies we are working at can increase the lifetime of generic compounds on the market as the compounds acquire better functional properties and a new brand name. The research department's studies concern the properties of individual active pharmaceutical ingredients (drug compounds / lead compounds) in biological media and crystals. We are also designing pharmaceutical systems for targeted delivery of drug molecules to their sites of action.

Key words: 
Biopolymers
Drug compounds
Membrane permeability
Pluronics
Polymorphism
Distribution
Solubility
Delivery systems
Cocrystals
Sublimation
Cyclodextrins
Cooperation: 

- South-West University "Neofit Rilski" (Blagoevgrad, Bulgaria);

- Indian Institute of Chemical Technology (IICT) (Hyderabad, India);

- Sat-sun Yen University (Guangzhou, China);

- Tianjin University of Technology (China);

- Beijing Institute of Technology (China);

- Shanghai Institute of Materia Medica, Chinese Academy of Sciences (Shanghai, China);

- University of Cape Town, Department of Chemistry, Center of Supramolecular Chemistry (Cape Town, Republic of South Africa);

- Institute of Pharmaceutics, University of Tromsø, (Norway);

- Institute of Chemical Sciences, University of Bologna (Italy);

- Biomedical Research Center (Borstel, Germany);

- Federal Institute for Materials Research and Testing (Berlin, Germany);

- Institute of Pharmaceutics, University of Helsinki (Finland);

- Pharmaceutical and Analytical R&D, AstraZeneca R&D (Molndal, Sweden);

- Institute of Pharmaceutics, University of Glasgow (Scotland);

- Institute of Physics and Chemistry, University of Southern Denmark (Odense, Denmark);

- Institute of Physiologically Active Substances, RAS (Chernogolovka);

- Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, RAS (Chernogolovka);

- Institute of General and Inorganic Chemistry, RAS (Moscow).

Publications: 

1. Perlovich G.L. Thermodynamic characteristics of cocrystal formation and melting points for rational design of pharmaceutical two-component systems // CrystEngComm. – 2015. – V. 17. – P. 7019 – 7028. DOI: 10.1039/c5ce00992h

2. Perlovich G.L. Prediction of solubility of two-component molecular crystals // CrystEngComm. - 2022. – V. 24. – Art. 2217 DOI: 10.1039/d2ce00105e

3. Surov A.O., Voronin A.P., Drozd K.V., Gruzdev M.S., Perlovich G.L., Prashanth J., Balasubramanian S. Polymorphic forms of antiandrogenic drug nilutamide: structural and thermodynamic aspects // Phys. Chem. Chem. Phys. -  2021. – V. 23(16). – P. 9695-9708. DOI: 10.1039/d1cp00793a.

4. Surov A.O., Churakov A.V., Perlovich G.L. Three Polymorphic Forms of Ciprofloxacin Maleate: Formation Pathways, Crystal Structures, Calculations and Thermodynamic Stability Aspects // Cryst. Growth Des. – 2016. – V. 16(11). – P. 6556-6567. DOI: 10.1021/acs.cgd.6b01277

5. Volkova T.V., Simonova O.R., Perlovich G.L. Another move towards bicalutamide dissolution and permeability improvement with acetylated beta-cyclodextrin solid dispersion // Pharmaceutics. – 2022. - V. 14(7). – Art. 1472. DOI: 10.3390/pharmaceutics14071472

6. Volkova T.V., Simonova O.R., Perlovich G.L. Permeability of diverse drugs through a lipid barrier: impact of pH and cyclodextrin // Journal of Molecular Liquids. – 2022. – V. 357(9). – Art. 115931. DOI: 10.1016/j.molliq.2022.11913

7. Blokhina S.V., Sharapova A.V., Ol’khovich M.V., Volkova T.V., Perlovich G.L., Solubility, lipophilicity and membrane permeability of some fluoroquinolone antimicrobials // Eur. J. Pharm. Sci. – 2016. – V. 105. – P. 29-37. DOI: 10.1016/j.ejps.2016.07.01

8. Blokhina S.V., Ol'khovich M.V., Sharapova A.V., Levshin I.B., Perlovich G.L. Thermodynamic insights to solubility and lipophilicity of new bioactive hybrids triazole with thiazolopyrimidines // J. Mol. Liq. – 2021. – Art. 114662. DOI: 10.1016/j.molliq.2020.114662.

9. Drozd, K.V., Manin A.N., Voronin A.P., Boycov D.E., Churakov A.V., Perlovich G.L. A combined experimental and theoretical study of miconazole salts and cocrystals: crystal structures, DFT computations, formation thermodynamics and solubility improvement // Phys. Chem. Chem. Phys. -  2021. - V. 23(21). – P.12456-12470. DOI: 10.1039/D1CP00956G

10. Drozd K.V., Manin A.N., Churakov A.V., Perlovich G.L. Novel Drug-Drug Cocrystal of Carbamazepine with para-Aminosalicylic Acid: Screening, Crystal Structure and Comparative Study of Carbamazepine Cocrystals Formation Thermodynamics // CrystEngComm. -  2017. - V. 19. – P. 4273-4286. DOI: 10.1039/C7CE00831G

Scientific and engineering bases of obtaining functional materials and nanocomposites

Head of the department: 
Agafonov Alexander Viktorovich
Scope of research: 

The aim of the studies is to develop new approaches to liquid phase synthesis of advanced functional materials based on natural and synthetic polymers and composites with nanoparticles and bioactive molecules as innovative industrially important materials.

Details:

- Developing new methods of obtaining composites based on polysaccharides and nanocrystalline cellulose with antimicrobic activity against Gram negative and Gram positive bacteria;

- Studying the effect of nanocrystalline cellulose as a composite component on calcium carbonate mineralization accompanied by the formation of various polymorphs for modelling biomineralization in polymer scaffolds applied in tissue engineering and regenerative medicine.

- Developing methods of modification of natural and synthetic polymers, including multicomponent compositions based on thermodynamic and structural studies of their solutions.

- Studying the effect of natural and synthetic polymers on the physicochemical properties of biologically active compounds.

- Developing methods of obtaining meso- and microporous nanostructured materials, porous carbon metal-containing composites, as well as magnetic adsorbents, photoactive materials, films, coatings, and membranes.

- Developing the scientific basis of plasma-chemical synthesis of hybrid nanomaterials based on polymers containing metal oxides and studying their adsorption, catalytic and bactericidal properties.

- Developing novel types of electrorheological gels and elastomers;

- Obtaining novel hybrid materials based on graphene, magnetic nanoparticles and molecular magnetics producing a strong magnetocaloric effect.

Key words: 
Biodegradable films
Silica hydrogels
Metal-organic frameworks
Plasma
Polymer composite
Ultrafiltration membranes
Delivery systems
Polymer gels
Host-guest complexes
Polymers and surfactants for pharmaceutical use
Natural, modified and polymeric cyclodextrins
Cooperation: 

- Ivanovo State University;

- Ufa Institute of Chemistry of Ufa Federal Research Centre of the Russian Academy of Sciences;

- Moscow Pedagogical State University;

- A.V.Topchiev Institute of Petrochemical Synthesis, RAS (Moscow);

- Mechanical Engineering Research Institute of the Russian Academy of Sciences (Moscow);

- All-Russian Research Institute of Starch and Processing of Starch-Containing Raw Materials (Moscow);

- A.N.Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences (Moscow);

- Saint Petersburg State University;

- Kazan (Volga Region) Federal University;

- University of Palermo, Italy;

- South-Central Minzu University,Wuhan, China;

- Ivanovo University of Chemistry and Technology, Russia;

- Ivanovo State Power Engineering University, Russia;

- V.N. Gorodkov Ivanovo Research Institute of Maternity and Childhood, Russia.

Publications: 

1. Ivanov K.V., Noskov A.V., Alekseeva O.V., Agafonov A.V. Synthesis of CaCu3Ti4O12: How Heat Treatment Influences Morphology and Dielectric Properties // RUSSIAN JOURNAL OF INORGANIC CHEMISTRY. – 2021. – Vol. 66. - No. 4. – P. 490-495. DOI: 10.1134/S0036023621300021.

2. Alekseeva O.V., Shibaeva V.D., Noskov A.V. Enhancing the thermal stability of ionogels: Synthesis and properties of triple ionic liquid/halloysite/mcc ionogels / [et al.] // MOLECULES. – 2021. – Vol. 26. - No. 20. DOI: 10.3390/molecules26206198.

3. Sirotkin N.A., Khlyustova A.V., Titov V.A., Agafonov A.V. The Use of a Novel Three-Electrode Impulse Underwater Discharge for the Synthesis of W-Mo Mixed Oxide Nanocomposites // Plasma Chemistry and Plasma Processing. – 2021. – V. 42. – P. 191–209. DOI: 10.1007/s11090-021-10213-3.

4. Alekseeva O.V., Noskov A.V., Titov V.A.  Adsorption performance of the polystyrene/montmorillonite composites: Effect of plasma treatment  // THE SCIENCE OF THE TOTAL ENVIRONMENT . – 2021. – Vol. 167. – P. 108505. DOI: 10.1016/j.cep.2021.108505.

5. Agafonov A.V., Grishina E.P., Kudryakova N.O.  Ionogels: Squeeze flow rheology and ionic conductivity of quasi-solidified nanostructured hybrid materials containing ionic liquids immobilized on halloysite // ARABIAN JOURNAL OF CHEMISTRY. – 2022. – Vol. 15. - No. 1. – P. 103470. DOI: 10.1016/j.arabjc.2021.103470.

6. Khlyustova A., Sirotkin N., Titov V., Agafonov A.  One-Pot Underwater Plasma Synthesis and Characterization of Fe- and Ni-Doped Boehmite // Crystal Research & Technology. – 2022. – Vol. 57. - No. 2. – P. 2100117. DOI: 10.1002/crat.202100117.

7. Алексеева О.В, Шипко М.Н., Смирнова Д.Н. и др. Модификация поверхности и физико-химических свойств алюмосиликатных нанотрубок галлуазита наночастицами магнетита // Поверхность. Рентгеновские, синхротронные и нейтронные исследования. – 2022. – № 3. – С. 23-30. DOI: 10.31857/S1028096022030025

8. Агафонов А.В., Сироткин Н. А., Титов В.А., Хлюстова А.В. Подводная низкотемпературная плазма как инструмент синтеза неорганических наноматериалов // Журнал неорганической химии. – 2022. – Т. 67. - № 3. – С. 271-280. DOI: 10.31857/S0044457X22030023.

9. Kochkina N., Nikitina M., Agafonov M., Delyagina E., Terekhova I. iota-Carrageenan hydrogels for methotrexate delivery // Journal of Molecular Liquids. - 2022. – Vol.  368. – P. 120790. DOI:10.1016/j.molliq.2022.120790.

10. Delyagina E., Garibyan A., Agafonov M., Terekhova I. Regularities of encapsulation of tolfenamic acid and some other non-steroidal anti-inflammatory drugs in metal organic frameworks on the basis of γ-cyclodextrin // Pharmaceutics. -  2023. V. 15(1). – P. 71. DOI: 10.3390/pharmaceutics15010071

Development of approaches and methods of physical chemistry for studying multicomponent supramolecular, molecular and ion-molecular systems as materials of the future

Head of the department: 
Kiselev Mikhail Grigorievich
Scope of research: 

- Gaining new knowledge about the physicochemical processes of formation of solution structure when predicting the behavior of liquid phase and fluid systems in response to external influences.

- Developing the theory of solutions and simulation approaches to describing liquid phase systems based on using computational chemistry methods and experimental studies of a variety of properties of multicomponent systems within a wide range of parameters of states including supercritical conditions.

- Establishing the regularities in the effect of the structure of compounds on their thermodynamic properties in multicomponent solutions to better study the mechanism of intermolecular interactions.

- Identifying the role of solvophobic effects on the physicochemical parameters of liquid phase systems within a wide range of pressure and temperature values. - Structural analysis of liquid phase and fluid systems based on modern methods of structural chemistry.

- Studying the effect of the composition of composite proton-conducting membranes based on polymers dopes with ionic liquids on their electrochemical and physicochemical properties.

- Based on dipyrromethene dyes obtaining new luminescent sensors, nanostructured biocompatible systems of delivery of biomarkers, photosensitizers, mono-/multilayer components of OLED devices with photoinduced electron transfer.

- Studying the interactions of biopolymers with macroheterocyclic compounds for medical purposes. - Finding regularities in interactions of macroheterocyclic and heteroaromatic compounds with biopolymers, establishing the effect of the nature of ligands on the strength of their binding with the polymer, ligand localization in the polymer in order to develop transport systems, sensors based on macroheterocyclic compounds and photothermosensitive polymer complexes based on polymers and heteroaromatic compounds.

- Synthesis of iron-containing dendrimer complexes based on spin equilibrium systems.

Key words: 
Supramolecular systems
Photoactive compounds
Polymorphism
Solvation
Supercritical fluids
Delivery systems
Machine learning
Cooperation: 

- Leipzig University (Germany);

- University of Coimbra (Portugal);

- University of Lille (Lille, France);

- Tianjin University (China);

- New York University Shanghai (China);

- Kazan Federal University (Kazan);

- Kazan State Medical University (Kazan);

- Zavoisky Physical Technical Institute (Kazan);

- Saint Petersburg State University (Saint Petersburg);

- A.N.Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences (Moscow);

- N. D. Zelinsky Institute of Organic Chemistry Russian Academy of Sciences (Moscow);

- Lobachevsky State University of Nizhny Novgorod (Nizhny Novgorod);

- Privolzhsky Research Medical University (Nizhny Novgorod);

- M.N. Mikheev Institute of Metal Physics of the Ural Branch of the Russian Academy of Sciences (Ekaterinburg);

- Ivanovo State University of Chemistry and Technology (Ivanovo);

- Nanomaterials Research Institute of Ivanovo State University (Ivanovo);

- Ivanovo State University (Ivanovo).

Publications: 

1. Barannikov V.P., Smirnov V.I., Kurbatova M.S. The thermochemical behavior of glycyl-L-histidine and β-alanyl-L-histidine peptides in (SDS + phosphate-buffered saline) micellar solution at pH = 7.4 // Journal of Molecular Liquids. – 2021. – V.331. – P. 115766. https://doi.org/10.1016/j.molliq.2021.115766

2. Khodov I.A. et al. Exploring the Conformational Equilibrium of Mefenamic Acid Released from Silica Aerogels via NMR Analysis // International Journal of Molecular Sciences. – 2023. – V.24. – P. 6882. https://doi.org/10.3390/ijms24086882

3. Oparin R.D. et al. Polymorphism and conformations of mefenamic acid in supercritical carbon dioxide // The Journal of Supercritical Fluids, – 2019. – V.152. – P. 104547. https://doi.org/10.1016/j.supflu.2019.104547

4. Bumagina N. A. et al. Basic structural modifications for improving the practical properties of BODIPY // Coordination Chemistry Reviews. – 2022. V. 469. P. 214684. https://doi.org/10.1016/j.ccr.2022.214684

5. Lebedeva N.S. et al. Theoretical and experimental study of interaction of macroheterocyclic compounds with ORF3a of SARS-CoV-2 // Scientific reports. – 2021. – V.11. – No 1. – P. 19481. https://doi.org/10.1038/s41598-021-99072-8

6. Gruzdev M. S., Chervonova U. V., Vorobeva V. E., Kolker A. M. Highly branched mesomorphic iron(III) complexes with a long alkyl fragments on periphery // Journal of Molecular Liquids. – 2020. – V. 320. – P. 114505. https://doi.org/10.1016/j.molliq.2020.114505

7. Shmukler L.E., Fedorova I.V., Fadeeva Yu. A., Safonova L.P. The physicochemical properties and structure of alkylammonium protic ionic liquids of RnH4-nNX (n = 1 – 3) family. A mini–review // Journal of Molecular Liquids. – 2021. – V. 321. – P. 114350. https://doi.org/10.1016/j.molliq.2020.114350

8. Ramenskaya L.M, Grishina E.P, Kudryakova N.O. Comparative study of atmospheric ionic liquids based on bis(trifluoromethylsulfonyl)imide anion and alkyl substituted cations of ammonium, pyrrolidinium and imidazolium // Journal of Molecular Liquids, – 2020. – V. 312. – P. 113368. V. 312, 113368. http://dx.doi.org/10.1016/j.molliq.2020.113368

9. Andrey V. Kustov et al. Monocationic Chlorin as a Promising Photosensitizer for Antitumor and Antimicrobial Photodynamic Therapy // Pharmaceutics – 2023. – V. 15. – P. 61. https://www.mdpi.com/1999-4923/15/1/61

10. Ksenofontov A.A et al. Accurate prediction of 11B NMR chemical shift of BODIPYs via machine learning // Physical Chemistry Chemical Physics. – 2023. – V.25. – P. 9472. https://pubs.rsc.org/en/content/articlehtml/2023/cp/d3cp00253e