Specifics of Pharmacokinetics and Biodistribution of 5-Fluorouracil Polymeric Complex.

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.

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

Cancer is a leading cause of mortality globally. Despite remarkable improvements in cancer-treatment approaches, disease recurrence and progression remain major obstacles to therapy. While chemotherapy is still a first-line treatment for a variety of cancers, the focus has shifted to the development and application of new approaches to therapy. Nevertheless, the relationship between immune response, neoplastic diseases and treatment efficiency is not fully understood. Therefore, the aim of the study was to investigate the immunopharmacological effects of methacrylic acid homopolymer in an in vivo tumor model. MATERIALS AND METHODS: Monomeric methacrylic acid was used to synthesize polymers. Methacrylic acid was polymerized in dioxane in the presence of 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid. To study the molecular weight characteristics of PMAA by GPC, carboxyl groups were preliminarily methylated with diazomethane. An experimental cancer model was obtained by grafting RMK1 breast cancer cells. The serum levels of IL-6, IL-10, IL-17, transforming growth factor ß1 (TGF-ß1), and tumor necrosis factor α (TNF-α) were measured by ELISA. RESULTS: The effect of PMAA on the serum concentrations of several cytokines was studied upon its single administration to laboratory animals in early neoplastic process. The IL-6, IL-17 and TGF-ß1 concentrations were found to change significantly and reach the level observed in intact rats. The IL-10 concentration tended to normalize. CONCLUSION: The positive results obtained are the basis for further studies on the effect of methacrylic-acid polymers with different molecular-weight characteristics on the neoplastic process.