%0 Journal Article
%@ 01677322
%A Moshikur, R.M.
%A Chowdhury, M.R.
%A Wakabayashi, R.
%A Tahara, Y.
%A Moniruzzaman, M.
%A Goto, M.
%D 2019
%F scholars:11692
%I Elsevier B.V.
%J Journal of Molecular Liquids
%K Biocompatibility; Body fluids; Cell culture; Cytotoxicity; Drug products; Esters; Ionic liquids; Lanthanum compounds; Mammals; Salts; Sodium; Solubility; Thermogravimetric analysis, Active pharmaceutical ingredients; Mammalian cell lines; Methotrexate; Methotrexate (MTX); Orders of magnitude; Phosphate-buffered salines; Simulated body fluids; Technological utility, Drug delivery
%P 226-233
%R 10.1016/j.molliq.2019.01.063
%T Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation
%U https://khub.utp.edu.my/scholars/11692/
%V 278
%X The technological utility of active pharmaceutical ingredients (APIs) is enormously improved when they are converted into ionic liquids (ILs). API-ILs possess better aqueous solubility and thermal stability than that of solid-state salt or crystalline drugs. However, many such API-ILs are not biocompatible or biodegradable. In the current study, we synthesized a series of IL-APIs using methotrexate (MTX), a potential anticancer prodrug, and biocompatible IL-forming cations (choline and amino acid esters). The MTX-IL moieties were characterized through 1 H NMR, FTIR, p-XRD, DSC and thermogravimetric analysis. The solubility of the MTX-ILs was evaluated in simulated body fluids (phosphate-buffered saline, simulated gastric, and simulated intestinal fluids). An assessment of the in vitro antitumor activity of the MTX-ILs in a mammalian cell line (HeLa cells) was used to evaluate their cytotoxicity. The MTX-ILs showed aqueous solubility at least 5000 times higher than that of free MTX and two orders of magnitude higher compared with that of a sodium salt of MTX in both water and simulated body fluids. Importantly, a proline ethyl ester MTX prodrug showed similar solubility as the MTX sodium salt but it provided improved in vitro antitumor activity. These results clearly suggest that the newly synthesized API-ILs represent promising potential drug formulations. © 2019 Elsevier B.V.
%Z cited By 58