eprintid: 11692
rev_number: 2
eprint_status: archive
userid: 1
dir: disk0/00/01/16/92
datestamp: 2023-11-10 03:26:13
lastmod: 2023-11-10 03:26:13
status_changed: 2023-11-10 01:15:52
type: article
metadata_visibility: show
creators_name: Moshikur, R.M.
creators_name: Chowdhury, M.R.
creators_name: Wakabayashi, R.
creators_name: Tahara, Y.
creators_name: Moniruzzaman, M.
creators_name: Goto, M.
title: Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation
ispublished: pub
keywords: 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
note: cited By 58
abstract: 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.
date: 2019
publisher: Elsevier B.V.
official_url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060078342&doi=10.1016%2fj.molliq.2019.01.063&partnerID=40&md5=f0ae32f5c42f31ba359006da8d75e5ef
id_number: 10.1016/j.molliq.2019.01.063
full_text_status: none
publication: Journal of Molecular Liquids
volume: 278
pagerange: 226-233
refereed: TRUE
issn: 01677322
citation:   Moshikur, R.M. and Chowdhury, M.R. and Wakabayashi, R. and Tahara, Y. and Moniruzzaman, M. and Goto, M.  (2019) Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation.  Journal of Molecular Liquids, 278.  pp. 226-233.  ISSN 01677322