Synergistic/antagonistic cytotoxic effects in mixtures of ionic liquids with doxorubicin or mitoxantrone

An NMR spectroscopy study of ionic liquid/drug systems at a molecular level and a scanning electron microscopy study in the liquid phase at a nano-scale level were applied for the first time to study ionic preparations of wellknown anticancer drugs. Cytotoxicity of binary mixtures of imidazolium ionic liquids with doxorubicin or mitoxantrone was studied in human colorectal adenocardnomaCaCo-2 cells, and the evidence of synergism/antagonism was assessed. Of the ten drug-containing mixtures tested, four demonstrated significant synergistic or antagonistic cytotoxic effects. These mixtures revealed distinct micro-structured patterns, as shown by scanning electron microscopy, whereas nuclear magnetic resonance evidenced the formation of strong interactions between the drug and the ionic liquid in some of the mixtures. Notably, all the test substances induced the cell death via necrosis in the Cato-2 cell line, thus revealing the dependence of the observed cytotoxic effects on the cell type. The observed synergistic effects suggested possible benefits of applying ionic liquids in drug formulations. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

This study applied NMR spectroscopy and scanning electron microscopy to investigate the interactions between ionic liquids and anticancer drugs, revealing synergistic or antagonistic cytotoxic effects in some mixtures. The observed cytotoxic effects were found to be cell type-dependent, with all test substances inducing cell death via necrosis in the CaCo-2 cell line. The study suggests potential benefits of utilizing ionic liquids in drug formulations.