Transport and toxicity of 5-fluorouracil, doxorubicin, and cyclophosphamide in in vitro placental barrier model based on BeWo b30 cells


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Abstract

An in vitro placental barrier model based on human choriocarcinoma BeWo b30 cell line was considered as a method of preclinical study of the transport and toxicity of antitumor agents and other organic compounds. Low permeabilities were found for 5-fluorouracil as an example of hydrophilic compound and for doxorubicin as an example of a lipophilic compound with a high degree of binding to proteins and DNA and a high permeability was found for cyclophosphamide as an example of lipophilic compound with a low degree of binding to proteins. Using impedance spectrometry and cell viability assessment via reduction of resazurin to resorufin, a pronounced cytotoxic effect of doxorubicin and good tolerance of 5-fluorouracil and cyclophosphamide by the cells were shown for drug concentrations equal to the maximum concentrations in the patients’ blood during the treatment of breast cancer.

About the authors

E. N. Knyazev

M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Scientific Research Center Bioclinicum; Far Eastern Federal University

Author for correspondence.
Email: e.knyazev@bioclinicum.com
Russian Federation, 16/10 ul. Miklukho-Maklaya, Moscow, 117997; Build. 85, 2ul. Ugreshskaya, Moscow, 115088; 8 ul. Sukhanova, Vladivostok, 690091

S. V. Nikulin

Scientific Research Center Bioclinicum; Far Eastern Federal University

Email: e.knyazev@bioclinicum.com
Russian Federation, Build. 85, 2ul. Ugreshskaya, Moscow, 115088; 8 ul. Sukhanova, Vladivostok, 690091

A. Yu. Khristichenko

Scientific Research Center Bioclinicum; D. Rogachev Federal Scientific and Clinical Center for Pediatric Hematology, Oncology, and Immunology

Email: e.knyazev@bioclinicum.com
Russian Federation, Build. 85, 2ul. Ugreshskaya, Moscow, 115088; 1 ul. Samory Machela, Moscow, 117997

T. N. Gerasimenko

Scientific Research Center Bioclinicum

Email: e.knyazev@bioclinicum.com
Russian Federation, Build. 85, 2ul. Ugreshskaya, Moscow, 115088

O. V. Kindeeva

Scientific Research Center Bioclinicum; Far Eastern Federal University

Email: e.knyazev@bioclinicum.com
Russian Federation, Build. 85, 2ul. Ugreshskaya, Moscow, 115088; 8 ul. Sukhanova, Vladivostok, 690091

V. A. Petrov

Scientific Research Center Bioclinicum; Institute of Nanotechnology of Microelectronics, Russian Academy of Sciences

Email: e.knyazev@bioclinicum.com
Russian Federation, Build. 85, 2ul. Ugreshskaya, Moscow, 115088; 32A Leninsky prosp., Moscow, 119991

G. A. Belyakova

I. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation

Email: e.knyazev@bioclinicum.com
Russian Federation, Build. 2, 8 Trubetskaya ul., Moscow, 119991

D. V. Maltseva

M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Scientific Research Center Bioclinicum

Email: e.knyazev@bioclinicum.com
Russian Federation, 16/10 ul. Miklukho-Maklaya, Moscow, 117997; Build. 85, 2ul. Ugreshskaya, Moscow, 115088


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