New Non-Toxic <i>N</i>-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs

In this work, we prepared new biocompatible <i>N</i>-alkyl cholinium-based ionic liquids to be used as cosolvents to improve the solubility of poorly water-soluble drugs, namely, sodium diclofenac and paracetamol. In this set of ionic liquids, we intend to understand the effect of increa...

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Autores principales:	Ana R. Jesus, Luís R. Raposo, Mário R. C. Soromenho, Daniela A. S. Agostinho, José M. S. S. Esperança, Pedro V. Baptista, Alexandra R. Fernandes, Patrícia M. Reis
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ionic liquids bioavailability oral drugs drug delivery cytotoxicity Mathematics QA1-939
Acceso en línea:	https://doaj.org/article/1f474b25575d413897627969fb2c2cb5
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spelling	oai:doaj.org-article:1f474b25575d413897627969fb2c2cb52021-11-25T19:06:22ZNew Non-Toxic <i>N</i>-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs10.3390/sym131120532073-8994https://doaj.org/article/1f474b25575d413897627969fb2c2cb52021-10-01T00:00:00Zhttps://www.mdpi.com/2073-8994/13/11/2053https://doaj.org/toc/2073-8994In this work, we prepared new biocompatible <i>N</i>-alkyl cholinium-based ionic liquids to be used as cosolvents to improve the solubility of poorly water-soluble drugs, namely, sodium diclofenac 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-dimensional <sup>1</sup>H/<sup>1</sup>H nuclear overhauser effect spectroscopy (NOESY) revealed an interaction between sodium diclofenac and the alaninate anion from the [C<sub>2</sub>Ch]<sub>2</sub>[SucAla]. In the case of paracetamol and [C<sub>4</sub>Ch][C<sub>2</sub>SO<sub>3</sub>], it was possible to observe two intermolecular interactions between the hydroxyl group of paracetamol and two protons from the cation [C<sub>4</sub>Ch]<sup>+</sup>. Interestingly, the ionic liquid bearing a succinyl-DL-alaninate anion, [SucAla]<sup>2−</sup>, and a <i>N</i>-ethyl cholinium cation, [C<sub>2</sub>Ch]<sup>+</sup>, 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.Ana R. JesusLuís R. RaposoMário R. C. SoromenhoDaniela A. S. AgostinhoJosé M. S. S. EsperançaPedro V. BaptistaAlexandra R. FernandesPatrícia M. ReisMDPI AGarticleionic liquidsbioavailabilityoral drugsdrug deliverycytotoxicityMathematicsQA1-939ENSymmetry, Vol 13, Iss 2053, p 2053 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ionic liquids bioavailability oral drugs drug delivery cytotoxicity Mathematics QA1-939
spellingShingle	ionic liquids bioavailability oral drugs drug delivery cytotoxicity Mathematics QA1-939 Ana R. Jesus Luís R. Raposo Mário R. C. Soromenho Daniela A. S. Agostinho José M. S. S. Esperança Pedro V. Baptista Alexandra R. Fernandes Patrícia M. Reis New Non-Toxic <i>N</i>-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs
description	In this work, we prepared new biocompatible <i>N</i>-alkyl cholinium-based ionic liquids to be used as cosolvents to improve the solubility of poorly water-soluble drugs, namely, sodium diclofenac 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-dimensional <sup>1</sup>H/<sup>1</sup>H nuclear overhauser effect spectroscopy (NOESY) revealed an interaction between sodium diclofenac and the alaninate anion from the [C<sub>2</sub>Ch]<sub>2</sub>[SucAla]. In the case of paracetamol and [C<sub>4</sub>Ch][C<sub>2</sub>SO<sub>3</sub>], it was possible to observe two intermolecular interactions between the hydroxyl group of paracetamol and two protons from the cation [C<sub>4</sub>Ch]<sup>+</sup>. Interestingly, the ionic liquid bearing a succinyl-DL-alaninate anion, [SucAla]<sup>2−</sup>, and a <i>N</i>-ethyl cholinium cation, [C<sub>2</sub>Ch]<sup>+</sup>, 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.
format	article
author	Ana R. Jesus Luís R. Raposo Mário R. C. Soromenho Daniela A. S. Agostinho José M. S. S. Esperança Pedro V. Baptista Alexandra R. Fernandes Patrícia M. Reis
author_facet	Ana R. Jesus Luís R. Raposo Mário R. C. Soromenho Daniela A. S. Agostinho José M. S. S. Esperança Pedro V. Baptista Alexandra R. Fernandes Patrícia M. Reis
author_sort	Ana R. Jesus
title	New Non-Toxic <i>N</i>-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs
title_short	New Non-Toxic <i>N</i>-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs
title_full	New Non-Toxic <i>N</i>-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs
title_fullStr	New Non-Toxic <i>N</i>-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs
title_full_unstemmed	New Non-Toxic <i>N</i>-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs
title_sort	new non-toxic <i>n</i>-alkyl cholinium-based ionic liquids as excipients to improve the solubility of poorly water-soluble drugs
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1f474b25575d413897627969fb2c2cb5
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New Non-Toxic <i>N</i>-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs

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