Immunopharmacological Properties of Methacrylic Acid Polymers as Potential Polymeric Carrier Constituents of Anticancer Drugs
Cytostatic chemotherapeutics provide a classical means to treat cancer, but conventional treatments have not increased in efficacy in the past years, warranting a search for new approaches to therapy. The aim of the study was, therefore, to obtain methacrylic acid (MAA) (co)polymers and to study the...
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2021-08-01
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author | Olga V. Zhukova Evgenia V. Arkhipova Tatyana F. Kovaleva Sergey A. Ryabov Irina. P. Ivanova Anna A. Golovacheva Daria A. Zykova Sergey D. Zaitsev |
author_facet | Olga V. Zhukova Evgenia V. Arkhipova Tatyana F. Kovaleva Sergey A. Ryabov Irina. P. Ivanova Anna A. Golovacheva Daria A. Zykova Sergey D. Zaitsev |
author_sort | Olga V. Zhukova |
collection | DOAJ |
description | Cytostatic chemotherapeutics provide a classical means to treat cancer, but conventional treatments have not increased in efficacy in the past years, warranting a search for new approaches to therapy. The aim of the study was, therefore, to obtain methacrylic acid (MAA) (co)polymers and to study their immunopharmacological properties. 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid (CDSPA) and 2-cyano-2-propyl dodecyl trithiocarbonate (CPDT) were used as reversible chain transfer agents. Experiments were carried out in Wistar rats. The MTT assay was used to evaluate the cytotoxic effect of the polymeric systems on peritoneal macrophages. An experimental tumor model was obtained by grafting RMK-1 breast cancer cells. Serum cytokine levels of tumor-bearing rats were analyzed. The chain transfer agents employed in classical radical polymerization substantially reduced the molecular weight of the resulting polymers, but a narrow molecular weight distribution was achieved only with CDSPA and high CPDT concentrations. Toxicity was not observed when incubating peritoneal macrophages with polymeric systems. In tumor-bearing rats, the IL-10 concentration was 1.7 times higher and the IL-17 concentration was less than half that of intact rats. Polymeric systems decreased the IL-10 concentration and normalized the IL-17 concentration in tumor-bearing rats. The maximum effect was observed for a MAA homopolymer with a high molecular weight. The anion-active polymers proposed as carrier constituents are promising for further studies and designs of carrier constituents of drug derivatives. |
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spelling | doaj.art-973bf25eda2944b2a46137d33470c97f2023-11-22T08:52:59ZengMDPI AGMolecules1420-30492021-08-012616485510.3390/molecules26164855Immunopharmacological Properties of Methacrylic Acid Polymers as Potential Polymeric Carrier Constituents of Anticancer DrugsOlga V. Zhukova0Evgenia V. Arkhipova1Tatyana F. Kovaleva2Sergey A. Ryabov3Irina. P. Ivanova4Anna A. Golovacheva5Daria A. Zykova6Sergey D. Zaitsev7Federal State Budgetary Educational Institution of Higher Education, Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603950 Nizhny Novgorod, RussiaFederal State Budgetary Educational Institution of Higher Education, Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603950 Nizhny Novgorod, RussiaFederal State Budgetary Educational Institution of Higher Education, Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603950 Nizhny Novgorod, RussiaDepartment of High-Molecular Compounds and Colloid Chemistry, National Research Lobachevsky State University, 603022 Nizhny Novgorod, RussiaDepartment of High-Molecular Compounds and Colloid Chemistry, National Research Lobachevsky State University, 603022 Nizhny Novgorod, RussiaDepartment of High-Molecular Compounds and Colloid Chemistry, National Research Lobachevsky State University, 603022 Nizhny Novgorod, RussiaFederal State Budgetary Educational Institution of Higher Education, Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603950 Nizhny Novgorod, RussiaDepartment of High-Molecular Compounds and Colloid Chemistry, National Research Lobachevsky State University, 603022 Nizhny Novgorod, RussiaCytostatic chemotherapeutics provide a classical means to treat cancer, but conventional treatments have not increased in efficacy in the past years, warranting a search for new approaches to therapy. The aim of the study was, therefore, to obtain methacrylic acid (MAA) (co)polymers and to study their immunopharmacological properties. 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid (CDSPA) and 2-cyano-2-propyl dodecyl trithiocarbonate (CPDT) were used as reversible chain transfer agents. Experiments were carried out in Wistar rats. The MTT assay was used to evaluate the cytotoxic effect of the polymeric systems on peritoneal macrophages. An experimental tumor model was obtained by grafting RMK-1 breast cancer cells. Serum cytokine levels of tumor-bearing rats were analyzed. The chain transfer agents employed in classical radical polymerization substantially reduced the molecular weight of the resulting polymers, but a narrow molecular weight distribution was achieved only with CDSPA and high CPDT concentrations. Toxicity was not observed when incubating peritoneal macrophages with polymeric systems. In tumor-bearing rats, the IL-10 concentration was 1.7 times higher and the IL-17 concentration was less than half that of intact rats. Polymeric systems decreased the IL-10 concentration and normalized the IL-17 concentration in tumor-bearing rats. The maximum effect was observed for a MAA homopolymer with a high molecular weight. The anion-active polymers proposed as carrier constituents are promising for further studies and designs of carrier constituents of drug derivatives.https://www.mdpi.com/1420-3049/26/16/4855(co)polymers of methacrylic acidmolecular weight characteristics of (co)polymersimmune systeminterleukinscytokines |
spellingShingle | Olga V. Zhukova Evgenia V. Arkhipova Tatyana F. Kovaleva Sergey A. Ryabov Irina. P. Ivanova Anna A. Golovacheva Daria A. Zykova Sergey D. Zaitsev Immunopharmacological Properties of Methacrylic Acid Polymers as Potential Polymeric Carrier Constituents of Anticancer Drugs Molecules (co)polymers of methacrylic acid molecular weight characteristics of (co)polymers immune system interleukins cytokines |
title | Immunopharmacological Properties of Methacrylic Acid Polymers as Potential Polymeric Carrier Constituents of Anticancer Drugs |
title_full | Immunopharmacological Properties of Methacrylic Acid Polymers as Potential Polymeric Carrier Constituents of Anticancer Drugs |
title_fullStr | Immunopharmacological Properties of Methacrylic Acid Polymers as Potential Polymeric Carrier Constituents of Anticancer Drugs |
title_full_unstemmed | Immunopharmacological Properties of Methacrylic Acid Polymers as Potential Polymeric Carrier Constituents of Anticancer Drugs |
title_short | Immunopharmacological Properties of Methacrylic Acid Polymers as Potential Polymeric Carrier Constituents of Anticancer Drugs |
title_sort | immunopharmacological properties of methacrylic acid polymers as potential polymeric carrier constituents of anticancer drugs |
topic | (co)polymers of methacrylic acid molecular weight characteristics of (co)polymers immune system interleukins cytokines |
url | https://www.mdpi.com/1420-3049/26/16/4855 |
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