{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T02:48:30Z","timestamp":1772765310111,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,31]],"date-time":"2021-10-31T00:00:00Z","timestamp":1635638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["IF\/00621\/2015"],"award-info":[{"award-number":["IF\/00621\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/Multi\/04378\/2020"],"award-info":[{"award-number":["UIDB\/Multi\/04378\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/CVT-EPI\/6685\/2014"],"award-info":[{"award-number":["PTDC\/CVT-EPI\/6685\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["ROTEIRO\/0031\/2013- PINFRA\/22161\/2016"],"award-info":[{"award-number":["ROTEIRO\/0031\/2013- PINFRA\/22161\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Symmetry"],"abstract":"<jats:p>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 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 1H\/1H nuclear overhauser effect spectroscopy (NOESY) 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 intermolecular 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\u2212, 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.<\/jats:p>","DOI":"10.3390\/sym13112053","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T22:17:23Z","timestamp":1635891443000},"page":"2053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["New Non-Toxic N-alkyl Cholinium-Based Ionic Liquids as Excipients to Improve the Solubility of Poorly Water-Soluble Drugs"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0840-6289","authenticated-orcid":false,"given":"Ana R.","family":"Jesus","sequence":"first","affiliation":[{"name":"LAQV, Requimte, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8637-346X","authenticated-orcid":false,"given":"Lu\u00eds R.","family":"Raposo","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2167-3813","authenticated-orcid":false,"given":"M\u00e1rio R. C.","family":"Soromenho","sequence":"additional","affiliation":[{"name":"LAQV, Requimte, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4740-3080","authenticated-orcid":false,"given":"Daniela A. S.","family":"Agostinho","sequence":"additional","affiliation":[{"name":"LAQV, Requimte, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9615-8678","authenticated-orcid":false,"given":"Jos\u00e9 M. S. S.","family":"Esperan\u00e7a","sequence":"additional","affiliation":[{"name":"LAQV, Requimte, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5255-7095","authenticated-orcid":false,"given":"Pedro V.","family":"Baptista","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2054-4438","authenticated-orcid":false,"given":"Alexandra R.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal"}]},{"given":"Patr\u00edcia M.","family":"Reis","sequence":"additional","affiliation":[{"name":"LAQV, Requimte, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,31]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Formulation Strategies to Improve the Bioavailability of Poorly Absorbed Drugs with Special Emphasis on Self-Emulsifying Systems","volume":"2013","author":"Gupta","year":"2013","journal-title":"ISRN Pharm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1039\/C6MD00358C","article-title":"Ionic liquids as a potential tool for drug delivery systems","volume":"7","author":"Adawiyah","year":"2016","journal-title":"MedChemComm"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ejpb.2015.04.034","article-title":"Transformation of acidic poorly water soluble drugs into ionic liquids","volume":"94","author":"Balk","year":"2015","journal-title":"Eur. 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