Design of pharmaceutical systems based on biopolymers and supramolecular complexes for the creation of bioavailable drugs

About the group:

Main problems:

Modern medicine involves the use of a wide range of drugs, which must have a specific set of properties necessary to reach the biological receptors. The main problem arising is the extremely low solubility of biologically active substances in physiological media. It is well known that bioavailability is one of the most important pharmacokinetic characteristics of a drug and is determined by the amount of active pharmaceutical ingredient (API) that has reached the systemic circulation. This value, in turn, directly depends on the kinetic and thermodynamic parameters of dissolution. No less important characteristic determining the bioavailability of a drug compound is permeability through the biological barriers (membranes of the intestinal epithelium, blood-brain barrier, etc.). In turn, lipophilicity, the measure of which is the distribution coefficient in the 1-octanol/water model system, makes it possible to estimate the permeability of a substance in a first approximation. Information on the solubility and permeability of candidate substances at the early stages of development is no less relevant than the affinity for the biological receptors. This is due, first of all, to the fact that solving the problem of low solubility at the final stages requires additional research and innovative technologies which makes the process of drug marketing very expensive. A number of approaches aimed at the solubility increasing have been created by now. First of all, this is a directed synthesis of leader compounds based on the search for correlations between the solubility and the crystal lattice structure of the substances in the groups of structural analogs. Secondly, it is the design of multicomponent crystals, the presence of additional components in the composition of which allows improving the properties of the main active pharmaceutical ingredient (API). A huge number of dosage forms are widely known, such as tablets, capsules, injections, suppositories, patches, ointments, etc. Besides the API, they contain various excipients, including those that increase solubility by enhancing the interaction with the solvent - the so-called solubilizers. Biopolymers and cyclodextrins containing the specific fragments exhibiting an affinity for poorly soluble substances and, as a consequence, promoting an increase in the API solubility, have found wide application as solubilizers. However, numerous studies have shown a decrease in the permeability of the biologically active compound in the presence of solubilizing agents. In such a situation, the problem of creating a bioavailable pharmaceutical product is solved by estimating the optimal (in terms of solubility and permeability) concentrations of a solubilizer.


Main directions of research:

- Design and studying the properties of solid dispersions based on active pharmaceutical ingredients (API) and various solubilizing agents;

- Development and studying the properties of supramolecular inclusion complexes in solids and solutions;

- Investigation of API sublimation processes and determination of the thermodynamic characteristics;

- Investigation of the dissolution, solvation, complexation and solubilization processes for API in the presence of solubilizing agents;

- In vitro study of membrane permeability of individual compounds through various types of artificial and synthetic membranes:

  • porous phospholipid membrane based on egg lecithin (PVPA);
  • membrane based on soy phosphatidylcholine (PermeapadTM);
  • membranes based on regenerated cellulose (MWCO 500, 12000-14000 Da).

- Study of the membrane permeability of APIs from solutions in equilibrium with solid dispersions, supramolecular inclusion complexes, and multicomponent crystals (co-crystals);

- Study of the distribution processes of API and supramolecular complexes in model solvent systems 1-octanol/buffer and n-hexane/buffer;

Assessment of the lipophilicity characteristics of compounds and the search for their relationship with membrane permeability;

- Development of the correlation models connecting the parameters of the dissolution, sublimation, solvation, permeability, distribution processes, and the biological activity - on the one hand, and physicochemical descriptors - on the other hand. Development of cluster models for predicting the pharmaceutical properties of individual compounds and complex systems.

- Examination of the influence of solubilizers (biopolymers, cyclodextrins) on the characteristics of solubility and permeability of multicomponent molecular crystals (co-crystals).


Research objects:

Potential neuroprotective agents:

1. 1,2,4-Thiadiazole derivatives:


2. Derivatives of adamantane and memantine


Sulfonamide derivatives:


Antifungal drugs and new compounds with antifungal activity:


Projects, Grants Laboratory:

Federal target program "Scientific and scientific-pedagogical personnel of innovative Russia for 2009–2013." State contract No. 02.740.11.0857. "Synthesis and design of molecular receptors and soluble forms of medicinal compounds based on methods and approaches of supramolecular chemistry." 2009-2013

Federal Target Program "Research and Development in Priority Areas of Development of the Scientific and Technological Complex of Russia for 2014 - 2020"

"Development of a multidisciplinary approach to the rational design of crystalline pharmaceutical compounds, ensuring high efficiency of their targeted delivery." No. 14.616.21.0027. 2014

Grant of the Russian Science Foundation "Development of scientific foundations for the creation of bioavailable drugs of a new generation using co-crystal technology on the example of anti-tuberculosis compounds." No. 14-13-00640. 2014-2016

RFBR grant "Relationship between the structure of new bicyclic non-aromatic isothiourea derivatives exhibiting neuroprotective properties with their specific activity, membrane permeability and solubility in biological media" No. 12-03-00019-a. 2012-2014

RFBR grant "Structural optimization of bicyclic non-aromatic derivatives of 2-amino-1,3-selenazines with neuroprotective and antioxidant action in order to correct the characteristics affecting bioavailability" No. 13-03-00348-a. 2013-2015

RFBR Grant No. 18-29-04023 (2018-2020) "Scientific bases for the production and functioning of metal-organic polymers based on cyclodextrins for the delivery and prolongation of the action of antirheumatic medicinal compounds"

Fundamental Research Program of the Presidium of the Russian Academy of Sciences No. 24. "Fundamental Foundations of the Technology of Nanostructures and Nanomaterials" Subprogram: III. Nanobiotechnology. No. 24. "Design of porphyrin-containing nanodrugs and their targeted delivery in order to regulate the concentration of nitric oxide in the blood." 2012-2014

7th EU Framework Program for Engineering and Natural Sciences (FP7-PEOPLE-2009-IRSES). Grant "Solvent effects on physico-chemical properties of bioactive compounds: combination of theory with experiments" No. PIRSES-GA-2009-247500. 2011-2013

RFBR grant "Multifunctional pharmaceutical systems for photodynamic cancer therapy: synthesis, stability, solubility and distribution in biological media" No. 14-03-00009. 2014-2016

Grant of the Russian Science Foundation "Development of new medicinal compounds with neuroprotective and cognitive-stimulating properties, using the approaches of supramolecular chemistry" No. 15-13-10017. 2015-2017

RFBR grant "Scientific bases for the production and functioning of metal-organic polymers based on cyclodextrins for the delivery and prolongation of the action of antirheumatic medicinal compounds" No. 18-29-04023 (2018-2020)

Grant of the Russian Science Foundation "Fundamental and applied aspects of the creation of bioavailable antifungal drugs." No. 19-13-00017. 2019-2021

Grant of the Russian Science Foundation “Design and research of new multicomponent crystalline forms of antihelmintic medicinal compounds. Joint Application of Experimental Approaches and Molecular Modeling Methods ”. No. 19-73-10005. 2019-2021

RFBR grant "Optimization of the parameters of activity, solubility and membrane permeability due to structural modification of amino derivatives of adamantane for the creation of bioavailable medicinal compounds." No. 19-53-18003 (Bolg_a) 2020-2021

Chapters in monographs:

1. Tatyana V. Volkova, Alexey N. Proshin and Irina V. Terekhova. Novel 1,2,4-Thiadiazole Derivatives: Biological and Physicochemical Properties and Their Improvement Using Cyclodextrins and Polymers. In " Thiadiazoles: Advances in Research and Applications". Ed. Alberto Cohen. Nova Science Publishers, Inc. 11.2020, 230 p. (PP. 101-173).  ISBN: 978-1-53618-878-3.

2. Artem O. Surov, Tatyana V. Volkova and German L. Perlovich. Design of Bioavailable Drugs on Basis of 1,2,4-Thiadiazoles: Solubility Improvement via Modification of Crystal Structure and Solvation Characteristics. In " Thiadiazoles: Advances in Research and Applications". Ed. Alberto Cohen. Nova Science Publishers, Inc. 11.2020, 230 p. (PP. 1-101). ISBN: 978-1-53618-878-3.

3. Perlovich G.L., Volkova T.V., Surov A.O. The processes of dissolution, distribution and membrane permeability of 1,2,4-tadiazoles: development of approaches to the creation of bioavailable medicinal compounds. // Chemistry of solutions of biologically active substances (Problems of chemistry of solutions) / Otv. ed. A.Yu. Tsivadze. - Ivanovo, 2016 .-- ISBN 978-5-904580-41-4


Journal articles 2018 - 2020:

1. Volkova, T. V., Simonova, O.R., Perlovich, G. L. (2021). Thiazolidine-2,4-dione derivative in 2-hydroxypropyl-β-cyclodextrin solutions: Complexation/solubilization, distribution and permeability, J. Mol. Liq. 333, 115931

2. Volkova, T. V., Levshin, I. B., Perlovich, G. L. (2020). New antifungal compound: Solubility thermodynamics and partitioning processes in biologically relevant solvents. Journal of Molecular Liquids, 310, 113148. doi:10.1016/j.molliq.2020.113148

3. Volkova, T. V., Perlovich, G. L. (2020). Comparative analysis of solubilization and complexation characteristics for new antifungal compound with cyclodextrins. Impact of cyclodextrins on distribution process. European Journal of Pharmaceutical Sciences, 154, 105531. doi:10.1016/j.ejps.2020.105531

4. Tatyana V. Volkova, Ksenia V. Drozd, Artem O. Surov. (2020). Effect of polymers and cyclodextrins on solubility, permeability and distribution of enzalutamide and apalutamide antiandrogens. J. Mol. Liq. 114937

5. Volkova, T., Surov, A., Terekhova, I. (2020). Metal–organic frameworks based on β-cyclodextrin: design and selective entrapment of non-steroidal anti-inflammatory drugs. Journal of Materials Science. 55, 13193–13205. doi:10.1007/s10853-020-04937-4

6. Perlovich, G. L., Volkova, T. V. (2020). Interrelation of Thermodynamic Sublimation Characteristics with Crystal Structure: Adamantane and Memantine Derivatives of Sulfonamide Molecular Crystals. CrystEngComm. 22, 2573-2584 doi:10.1039/d0ce00108b

7. Kritskiy, I., Volkova, T., Sapozhnikova, T., Mazur, A., Tolstoy, P., Terekhova, I. (2020). Methotrexate-loaded metal-organic frameworks on the basis of γ-cyclodextrin: Design, characterization, in vitro and in vivo investigation. Materials Science and Engineering: C, 111, 110774. doi:10.1016/j.msec.2020.110774

8. A. N. Manin, K. V. Drozd, A. O. Surov, C. Andrei, T. V. Volkova, G. L. Perlovich. (2020). Identification of a previously unreported co-crystal form of acetazolamide: a combination of multiple experimental and virtual screening methods. Phys. Chem. Chem. Phys. 22, 20867-20879 doi:10.1039/D0CP02700F

9. Tencheva, A., Liu, R., Volkova, T. V., Chayrov, R., Mitrev, Y., Štícha, M., Yuhuan Li, Hailun Jiang, Zhuorong Li, Ivanka Stankova, Perlovich, G. L. (2020). Synthetic analogues of memantine as neuroprotective and influenza viral inhibitors: in vitro and physicochemical studies. Amino Acids. 52, 1559-1580. doi:10.1007/s00726-020-02914-4

10. Volkova T.V., Domanina E.N., Chislov M.V., Proshin A.N., Terekhova I.V. (2020). Polymeric composites of 1,2,4-thiadiazole: solubility, dissolution and permeability assay. Therm. Anal. Calorim.  140, 2305–2315

11. Volkova T., Kumeev R., Kochkina N., Terekhova I. (2019) Impact of Pluronics of different structure on pharmacologically relevant properties of sulfasalazine and methotrexate. J. Mol. Liq. 289, 111076

12. Agafonov M., Volkova T., Kumeev R., Chibunova E., Terekhova I. (2019). Impact of pluronic F127 on aqueous solubility and membrane permeability of antirheumatic compounds of different structure and polarity. J.Mol. Liq. 274, 770-777.

13. Kritskiy I., Volkova T., Surov A., Terekhova I. (2019). γ-Cyclodextrin-metal organic frameworks as efficient microcontainers for encapsulation of leflunomide and acceleration of its transformation into teriflunomide // Carbohydr. Polym. 216, 224-230

14. Voronin, A. P., Volkova, T. V., Ilyukhin, A., Proshin, A. N., & Perlovich, G. L. (2020). Substituent Effect on the Packing Architecture of Adamantane and Memantine Derivatives of Sulfonamide Molecular Crystals. : CrystEngComm. 22, 349. doi:10.1039/c9ce01750j

15. Perlovich, G. L., Volkova, T. V. (2020). Interrelation of Thermodynamic Sublimation Characteristics with Crystal Structure: Adamantane and Memantine Derivatives of Sulfonamide Molecular Crystals. CrystEngComm, 2020, 1-3. doi:10.1039/d0ce00108b

16. Volkova, T. V., Domanina, E. N., Kumeev, R. S., Proshin, A. N., Terekhova, I. V. (2018). The effect of different polymers on the solubility, permeability and distribution of poor soluble 1,2,4-thiadiazole derivative. Journal of Molecular Liquids, 269, 492–500. doi:10.1016/j.molliq.2018.08.062

17. Kritskiy, I., Kumeev, R., Volkova, T., Shipilov, D., Kutyasheva, N., Grachev, M., & Terekhova, I. (2018). Selective binding of methotrexate to monomeric, dimeric and polymeric cyclodextrins. New Journal of Chemistry, 42(17), 14559–14567. doi:10.1039/c8nj02632g

18. Voronin, A. P., Volkova, T. V., Ilyukhin, A. B., Trofimova, T. P., Perlovich, G. L. (2018). Structural and energetic aspects of adamantane and memantine derivatives of sulfonamide molecular crystals: experimental and theoretical characterisation. CrystEngComm, 20(25), 3476–3489. doi:10.1039/c8ce00426a

19. Perlovich, G. L., Volkova, T. V. (2018). Sublimation thermodynamics aspects of adamantane and memantine derivatives of sulfonamide molecular crystals. Physical Chemistry Chemical Physics, 20(30), 19784–19791. doi:10.1039/c8cp03716g


UV/VIS спектрофотометр УФ и видимой области
UV/VIS спектрофотометр УФ и видимой области