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...

Full description

Bibliographic Details
Main Authors: Olga V. Zhukova, Evgenia V. Arkhipova, Tatyana F. Kovaleva, Sergey A. Ryabov, Irina. P. Ivanova, Anna A. Golovacheva, Daria A. Zykova, Sergey D. Zaitsev
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/16/4855
_version_ 1827684590567817216
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.
first_indexed 2024-03-10T08:33:22Z
format Article
id doaj.art-973bf25eda2944b2a46137d33470c97f
institution Directory Open Access Journal
issn 1420-3049
language English
last_indexed 2024-03-10T08:33:22Z
publishDate 2021-08-01
publisher MDPI AG
record_format Article
series Molecules
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
work_keys_str_mv AT olgavzhukova immunopharmacologicalpropertiesofmethacrylicacidpolymersaspotentialpolymericcarrierconstituentsofanticancerdrugs
AT evgeniavarkhipova immunopharmacologicalpropertiesofmethacrylicacidpolymersaspotentialpolymericcarrierconstituentsofanticancerdrugs
AT tatyanafkovaleva immunopharmacologicalpropertiesofmethacrylicacidpolymersaspotentialpolymericcarrierconstituentsofanticancerdrugs
AT sergeyaryabov immunopharmacologicalpropertiesofmethacrylicacidpolymersaspotentialpolymericcarrierconstituentsofanticancerdrugs
AT irinapivanova immunopharmacologicalpropertiesofmethacrylicacidpolymersaspotentialpolymericcarrierconstituentsofanticancerdrugs
AT annaagolovacheva immunopharmacologicalpropertiesofmethacrylicacidpolymersaspotentialpolymericcarrierconstituentsofanticancerdrugs
AT dariaazykova immunopharmacologicalpropertiesofmethacrylicacidpolymersaspotentialpolymericcarrierconstituentsofanticancerdrugs
AT sergeydzaitsev immunopharmacologicalpropertiesofmethacrylicacidpolymersaspotentialpolymericcarrierconstituentsofanticancerdrugs