TY - JOUR
T1 - Ionic Levothyroxine Formulations
T2 - Synthesis, Bioavailability, and Cytotoxicity Studies
AU - Barreira, António
AU - Santos, Andreia F. M.
AU - Dionísio, Madalena
AU - Jesus, Ana R.
AU - Duarte, Ana Rita C.
AU - Petrovski, Željko
AU - Paninho, Ana B.
AU - Ventura, Márcia G.
AU - Branco, Luís C.
N1 - info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50006%2F2020/PT#
info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FEAM-AMB%2F2023%2F2021/PT#
Funding Information:
Ana R. Jesus and Ana Rita C. Duarte acknowledge the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme, under grant agreement No ERC-2016-CoG 725034.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/5/16
Y1 - 2023/5/16
N2 - Thyroid diseases affect a considerable portion of the population, with hypothyroidism being one of the most commonly reported thyroid diseases. Levothyroxine (T4) is clinically used to treat hypothyroidism and suppress thyroid stimulating hormone secretion in other thyroid diseases. In this work, an attempt to improve T4 solubility is made through the synthesis of ionic liquids (ILs) based on this drug. In this context, [Na][T4] was combined with choline [Ch]+ and 1-(2-hydroxyethyl)-3-methylimidazolium [C2OHMiM]+ cations in order to prepare the desired T4-ILs. All compounds were characterized by NMR, ATR-FTIR, elemental analysis, and DSC, aiming to check their chemical structure, purities, and thermal properties. The serum, water, and PBS solubilities of the T4-ILs were compared to [Na][T4], as well as the permeability assays. It is important to note an improved adsorption capacity, in which no significant cytotoxicity was observed against L929 cells. [C2OHMiM][T4] seems to be a good alternative to the commercial levothyroxine sodium salt with promising bioavailability.
AB - Thyroid diseases affect a considerable portion of the population, with hypothyroidism being one of the most commonly reported thyroid diseases. Levothyroxine (T4) is clinically used to treat hypothyroidism and suppress thyroid stimulating hormone secretion in other thyroid diseases. In this work, an attempt to improve T4 solubility is made through the synthesis of ionic liquids (ILs) based on this drug. In this context, [Na][T4] was combined with choline [Ch]+ and 1-(2-hydroxyethyl)-3-methylimidazolium [C2OHMiM]+ cations in order to prepare the desired T4-ILs. All compounds were characterized by NMR, ATR-FTIR, elemental analysis, and DSC, aiming to check their chemical structure, purities, and thermal properties. The serum, water, and PBS solubilities of the T4-ILs were compared to [Na][T4], as well as the permeability assays. It is important to note an improved adsorption capacity, in which no significant cytotoxicity was observed against L929 cells. [C2OHMiM][T4] seems to be a good alternative to the commercial levothyroxine sodium salt with promising bioavailability.
KW - cytotoxicity
KW - ionic formulations
KW - levothyroxine (T4)
KW - permeability
KW - solubility
KW - T4 based ionic liquids (T4-ILs)
UR - http://www.scopus.com/inward/record.url?scp=85160379631&partnerID=8YFLogxK
U2 - 10.3390/ijms24108822
DO - 10.3390/ijms24108822
M3 - Article
C2 - 37240166
AN - SCOPUS:85160379631
SN - 1661-6596
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 10
M1 - 8822
ER -