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One of the promising and relevant directions in the treatment of oncological diseases is currently the development of a system for the delivery of antitumor drugs based on polyanions. Therefore, the aim of this work was to study the specifics of pharmacokinetics and biodistribution of a 5-Fluorouracil polymeric complex compared with commercial 5-Fluorouracil., Materials and Methods: Monomeric methacrylic acid was used to synthesize polymers; 2-phenylpropane-2-ilbenzodithioate was used for the synthesis of poly(methacrylic acid). To study the molecular-weight characteristics of poly(methacrylic acid) by gel permeation chromatography, an experimental neoplasm model was obtained by grafting PC-1 cancer cells. Blood samples were drawn from the tail vein at different points in time. The rats were sacrificed via decapitation after drawing the last pharmacokinetic blood sample. To study the biodistribution, internal organs were isolated and analyzed. The measurements were carried out by high-performance liquid chromatography., Results: Our results demonstrate that incorporation in a polymeric complex changes the pharmacokinetics and biodistribution profile of 5-FU. The polymeric complex was shown to accumulate to a higher level in the lung and spleen., Conclusion: The results obtained are the basis for further studies to verify the efficacy of the 5-Fluorouracil polymeric complex.

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.

The relative monomer reactivities in the reversible addition-fragmentation chain transfer (RAFT) radical copolymerization of styrene (S) and acrylic acid (AA) in a solution of the polar solvent N , N -dimethylformamide are found to be dependent on the chemical nature of the RAFT agent. Polymeric RAFT agents based on polyacrylic acid enhance the difference in monomer reactivities (dithiobenzoate - r AA = 0.09 ± 0.02, r S = 3.5 ± 1.2, trithiocarbonate - r AA = 0.08 ± 0.04, r S = 3.03 ± 1.78) compared to low molecular weight RAFT agents (dibenzyl dithiobenzoate - r AA = 0.14 ± 0.01, r S = 1.00 ± 0.01, dibenzyl trithiocarbonate - r AA = 0.08 ± 0.01, r S = 0.85 ± 0.03). The opposite effect on the relative reactivity of acrylic acid is observed when polymeric RAFT agents based on polystyrene are used (dithiobenzoate - r AA = 3.3 ± 0.4, r S = 0.72 ± 0.05, trithiocarbonate - r AA = 0.11 ± 0.01, r S = 0.54 ± 0.03). In all the investigated systems the copolymers formed are characterized by narrow MWD due to the high efficiency of the chosen RAFT agents., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)