TY - JOUR
T1 - New non-toxic n-alkyl cholinium-based ionic liquids as excipients to improve the solubility of poorly water-soluble drugs
AU - Jesus, Ana R.
AU - Raposo, Luís R.
AU - Soromenho, Mário R.C.
AU - Agostinho, Daniela A. S.
AU - Esperança, José M. S. S.
AU - Baptista, Pedro V.
AU - Fernandes, Alexandra R.
AU - Reis, Patrícia M.
N1 - info:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00621%2F2015%2FCP1284%2FCT0002/PT#
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/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT#
info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FCVT-EPI%2F6685%2F2014/PT#
LA/P/0140/2020
ROTEIRO/0031/2013—PINFRA/22161/2016
PY - 2021/11
Y1 - 2021/11
N2 - In this work, we prepared new biocompatible N-alkyl cholinium-based ionic liquids to be used as cosolvents to improve the solubility of poorly water-soluble drugs, namely, sodium diclo-fenac and paracetamol. In this set of ionic liquids, we intend to understand the effect of increasing the asymmetry of the ionic liquid cation/anion by growing the length of one of the alkyl chains attached to the nitrogen center/sulfonate center on the dissolution capacity of the ionic liquid. The addition of these new ionic liquids to water increased the dissolution capacity of the drugs up to four-times that in water, and improved the pharmacodynamic properties of these drugs, especially the case of sodium diclofenac. The intermolecular interactions between the drugs and ionic liquids were investigated by NMR. Two-dimensional1H/1H nuclear overhauser effect spectroscopy (NO-ESY) revealed an interaction between sodium diclofenac and the alaninate anion from the [C2Ch]2[SucAla]. In the case of paracetamol and [C4Ch][C2SO3], it was possible to observe two inter-molecular interactions between the hydroxyl group of paracetamol and two protons from the cation [C4Ch]+. Interestingly, the ionic liquid bearing a succinyl-DL-alaninate anion, [SucAla]2−, and a N-ethyl cholinium cation, [C2Ch]+, which presented the highest ability to dissolve sodium diclofenac, showed no cytotoxicity up to 500 mM. Therefore, this ionic liquid is a potential candidate for drug delivery applications.
AB - In this work, we prepared new biocompatible N-alkyl cholinium-based ionic liquids to be used as cosolvents to improve the solubility of poorly water-soluble drugs, namely, sodium diclo-fenac and paracetamol. In this set of ionic liquids, we intend to understand the effect of increasing the asymmetry of the ionic liquid cation/anion by growing the length of one of the alkyl chains attached to the nitrogen center/sulfonate center on the dissolution capacity of the ionic liquid. The addition of these new ionic liquids to water increased the dissolution capacity of the drugs up to four-times that in water, and improved the pharmacodynamic properties of these drugs, especially the case of sodium diclofenac. The intermolecular interactions between the drugs and ionic liquids were investigated by NMR. Two-dimensional1H/1H nuclear overhauser effect spectroscopy (NO-ESY) revealed an interaction between sodium diclofenac and the alaninate anion from the [C2Ch]2[SucAla]. In the case of paracetamol and [C4Ch][C2SO3], it was possible to observe two inter-molecular interactions between the hydroxyl group of paracetamol and two protons from the cation [C4Ch]+. Interestingly, the ionic liquid bearing a succinyl-DL-alaninate anion, [SucAla]2−, and a N-ethyl cholinium cation, [C2Ch]+, which presented the highest ability to dissolve sodium diclofenac, showed no cytotoxicity up to 500 mM. Therefore, this ionic liquid is a potential candidate for drug delivery applications.
KW - Bioavailability
KW - Cytotoxicity
KW - Drug delivery
KW - Ionic liquids
KW - Oral drugs
UR - http://www.scopus.com/inward/record.url?scp=85118502967&partnerID=8YFLogxK
U2 - 10.3390/sym13112053
DO - 10.3390/sym13112053
M3 - Article
AN - SCOPUS:85118502967
SN - 2073-8994
VL - 13
JO - Symmetry
JF - Symmetry
IS - 11
M1 - 2053
ER -