Immunopharmacological Properties of Methacrylic Acid Polymers as Potential Polymeric Carrier Constituents of Anticancer Drugs

Abstract

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.

Effect of Poly(methacrylic acid) on the Cytokine Level in an In Vivo Tumor Model

“…Earlier we proposed a scheme of the influence of IL-10 and IL-17 on the tumor process [ 57 ]. IL-10 promotes conversion of M1 macrophages (classically activated, with phagocytosis as a main function) to M2 macrophages (alternatively activated macrophages, TAMs, which facilitate tumor cell evasion from the immune system) [ 58 ].…”

Specifics of Pharmacokinetics and Biodistribution of 5-Fluorouracil Polymeric Complex

“…Polymeric particles are of interest in this direction, given the fact that they are used as carriers for antitumor agents. In the course of this study, an assessment of a polymeric complex based on low-molecular-weight PMAA was carried out, for which an immunopharmacological effect is noted [30,40,[47][48][49].…”

“…Various polymeric carriers to deliver anticancer agents are developed and investigated by many research teams worldwide [29,30].…”

Kollicoat MAE® 100P as a film former polymer for nanoparticles preparation

“…Another highlighted characteristic of the Kollicoat MAE® 100P is the innocuousness. Synthetic polymers and copolymers based on methacrylic acid tested as drug carriers of different drugs do not exert either toxic effects or changes in the metabolic activity of immune system cells [30]. The innocuity was also observed in immunogenicity studies performed on coated tablets with methacrylic acid.…”