Transport and toxicity of 5-fluorouracil,doxorubicin, and cyclophosphamide in in vitro placental barrier model based on BeWo b30 cells |
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Authors: | Knyazev E N Nikulin S V Khristichenko A Yu Gerasimenko T N Kindeeva O V Petrov V A Belyakova G A Maltseva D V |
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Institution: | 1.M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 ul. Miklukho-Maklaya, 117997, Moscow, Russian Federation ;2.Scientific Research Center Bioclinicum, Build. 85, 2ul. Ugreshskaya, 115088, Moscow, Russian Federation ;3.Far Eastern Federal University, 8 ul. Sukhanova, 690091, Vladivostok, Russian Federation ;4.D. Rogachev Federal Scientific and Clinical Center for Pediatric Hematology, Oncology, and Immunology, 1 ul. Samory Machela, 117997, Moscow, Russian Federation ;5.Institute of Nanotechnology of Microelectronics, Russian Academy of Sciences, 32A Leninsky prosp., 119991, Moscow, Russian Federation ;6.I. M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Build. 2, 8 Trubetskaya ul., 119991, Moscow, Russian Federation ; |
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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. |
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