Modeling of ex vivo internalization method of water- Soluble anticancer drugs in small intestine using chemiluminescence [МОДЕЛИРОВАНИЕ ИНТЕРНАЛИЗАЦИИ ВОДОРАСТВОРИМЫХ пРОТИВООпУХОЛЕВЫХ ЦИТОСТАТИКОВ В ТОНКОЙ КИШКЕ ЭКСпРЕСС-МЕТОДОМ EX VIVO С пОМОЩЬЮ ХЕМИЛЮМИНЕСЦЕНЦИИ]

Introduction. the ability of the small intestine (internalization) to absorb water-soluble anticancer cytostatics determines the possibility of their oral administration. the ex-vivo express method that simulates the internalization of substances using a modified technique of an isolated «inverted» segment of the rat small intestine with flash chemiluminescence is adequate to solve the problem. Objectives: to evaluate the absorption of the new water-soluble anticancer cytostatics with different properties from the rat small intestine for preclinical study by oral administration. material and methods. conjugated with acridinium (Acridinium NHS Ester, Toronto Research Chemicals, Canada) cytostatics were studied: low molecular weight (1) anthrafuran-acridinium (MW 0.8 kDa) and high molecular weight (2) aimpila-acridinium (MW 105 kDa) and (3) L-lysine-α-oxidase (LO-acridinium, MW 122 kDa). absorption was determined in a modified model of an isolated «inverted» segment of the rat small intestine using flash-chemiluminescence with the calculation of the relative light units (RLu). Results. It was shown that the absorption level of acridinium-conjugated cytostatics depending on molar concentration ranged from 55 % (1) to 1.7-11 % (2, 3) and 2500 (1) to 9.2-188 nmol/l (2, 3), respectively. the level of internalized anthrafuran-acridinium (55 %) was consistent with the known value of the effective non-conjugated cytostatic oral dose, which was two times higher than equitherapeutical parenteral dose: 100 mg/kg vs 50 mg/kg. Conclusion. the data obtained allow us to consider ex vivo express method for preclinical study of the various water-soluble anticancer cytostatics for screening and identification of an opportunity for oral administration and estimation of starting dose. the method has a good correlation with in vivo tests and economically favorable due to a quick response and small number of the tested agent. © 2019 Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved.

Treshalina H.M. 1 , Andronova N.V.2 , Tcherkassova J.R.1 , Tsurkan S.A.2 , Klinski E.Yu.2 , Lukasheva E.V. 3 , Babayeva G. 3 , Treshchalin M.I.4
Tomsk National Research Medical Center of the Russian Academy of Sciences
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  • 1 N.N. Blokhin National Medical Research center of Oncology, Ministry of Health of Russia, 24, Kashirskoye shosse, Moscow, 115548, Russian Federation
  • 2 «JVs Diagnostics LLC», Skolkovo Innovation Center, B. Boulevard 42, Moscow, 143026, Russian Federation
  • 3 Peoples' Friendship University of Russia, 6, Miklukho-Maklaya street, Moscow, 117198, Russian Federation
  • 4 Gause Institute of New Antibiotics, 11, Pirogovskaya street, Moscow, 119021, Russian Federation
Cytostatics; Ex vivo; Express-method; Internalization; Rat small intestine
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