Specifics of Pharmacokinetics and Biodistribution of 5-Fluorouracil Polymeric Complex

Author:

Zhukova Olga V.1ORCID,Dubovskaya Natalya A.1ORCID,Zykova Daria A.1,Arkhipova Evgenia V.1ORCID,Vorobeva Olga A.1ORCID,Zaborskaya Olga G.1,Zaitsev Sergey D.2,Grigoreva Alexandra O.2,Chicharov Aleksandr A.2,Ryabov Sergey A.2

Affiliation:

1. Department of Pharmaceutical Chemistry and Pharmacognosy, Federal State Budgetary Educational Institution of Higher Education, Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, 603950 Nizhny Novgorod, Russia

2. Department of High-Molecular Compounds and Colloid Chemistry, National Research Lobachevsky State University, 603022 Nizhny Novgorod, Russia

Abstract

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.

Funder

Priority-2030 program

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

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