Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs
New dicationic ionic liquids (DcILs) based on carboxylic acid-derived, N-acetyl amino acid-derived or bromide anions, and ammonium cations were synthesized and characterized. DcILs were employed as co-solvents to improve the solubility of ibuprofen and ketoprofen belonging to BCS class II. These DcI...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Journal of Ionic Liquids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772422023000046 |
| _version_ | 1797801630425415680 |
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| author | Ana B.P. Silva Ana R. Jesus Daniela A.S. Agostinho José M.S.S. Esperança Alexandre Paiva Ana R.C. Duarte Patrícia M. Reis |
| author_facet | Ana B.P. Silva Ana R. Jesus Daniela A.S. Agostinho José M.S.S. Esperança Alexandre Paiva Ana R.C. Duarte Patrícia M. Reis |
| author_sort | Ana B.P. Silva |
| collection | DOAJ |
| description | New dicationic ionic liquids (DcILs) based on carboxylic acid-derived, N-acetyl amino acid-derived or bromide anions, and ammonium cations were synthesized and characterized. DcILs were employed as co-solvents to improve the solubility of ibuprofen and ketoprofen belonging to BCS class II. These DcILs demonstrated to be less cytotoxic towards fibroblasts L929 cells and contributed to an augment in the solubility of both drugs when compared with monocationic ionic liquids (McILs). The cytotoxic profile of some of these ILs was established, and when the linker between two ammonium cations was an ether group or a short alkyl chain an IC50 higher than 200 mM for fibroblasts L929 cells was achieved.The anion structure showed to be a key factor in the solubility of both drugs, being the family of carboxylic acid-derived, the one that presented the most significant effect, followed by N-acetyl amino acid-derived and finally bromide. The two dimensional 1H1H– NOESY NMR spectra showed the interaction between the IL and the two oral drugs, responsible for the improvement of their solubility. The lipophilicity (logP) of ibuprofen and ketoprofen reduced in the presence of these new DcILs. |
| first_indexed | 2024-03-13T04:53:23Z |
| format | Article |
| id | doaj.art-490fbcfabdd1440fab399237c0b20344 |
| institution | Directory Open Access Journal |
| issn | 2772-4220 |
| language | English |
| last_indexed | 2024-03-13T04:53:23Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Ionic Liquids |
| spelling | doaj.art-490fbcfabdd1440fab399237c0b203442023-06-18T05:04:09ZengElsevierJournal of Ionic Liquids2772-42202023-06-0131100052Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugsAna B.P. Silva0Ana R. Jesus1Daniela A.S. Agostinho2José M.S.S. Esperança3Alexandre Paiva4Ana R.C. Duarte5Patrícia M. Reis6LAQV, Requimte, Departamento de Química, Nova School of Science and Technology, Caparica, 2829-516, PortugalLAQV, Requimte, Departamento de Química, Nova School of Science and Technology, Caparica, 2829-516, PortugalLAQV, Requimte, Departamento de Química, Nova School of Science and Technology, Caparica, 2829-516, PortugalLAQV, Requimte, Departamento de Química, Nova School of Science and Technology, Caparica, 2829-516, PortugalLAQV, Requimte, Departamento de Química, Nova School of Science and Technology, Caparica, 2829-516, PortugalCorresponding author.; LAQV, Requimte, Departamento de Química, Nova School of Science and Technology, Caparica, 2829-516, PortugalCorresponding author.; LAQV, Requimte, Departamento de Química, Nova School of Science and Technology, Caparica, 2829-516, PortugalNew dicationic ionic liquids (DcILs) based on carboxylic acid-derived, N-acetyl amino acid-derived or bromide anions, and ammonium cations were synthesized and characterized. DcILs were employed as co-solvents to improve the solubility of ibuprofen and ketoprofen belonging to BCS class II. These DcILs demonstrated to be less cytotoxic towards fibroblasts L929 cells and contributed to an augment in the solubility of both drugs when compared with monocationic ionic liquids (McILs). The cytotoxic profile of some of these ILs was established, and when the linker between two ammonium cations was an ether group or a short alkyl chain an IC50 higher than 200 mM for fibroblasts L929 cells was achieved.The anion structure showed to be a key factor in the solubility of both drugs, being the family of carboxylic acid-derived, the one that presented the most significant effect, followed by N-acetyl amino acid-derived and finally bromide. The two dimensional 1H1H– NOESY NMR spectra showed the interaction between the IL and the two oral drugs, responsible for the improvement of their solubility. The lipophilicity (logP) of ibuprofen and ketoprofen reduced in the presence of these new DcILs.http://www.sciencedirect.com/science/article/pii/S2772422023000046Dicationic ionic liquidsSolubilityCytotoxicityDrug deliveryBioavailability |
| spellingShingle | Ana B.P. Silva Ana R. Jesus Daniela A.S. Agostinho José M.S.S. Esperança Alexandre Paiva Ana R.C. Duarte Patrícia M. Reis Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs Journal of Ionic Liquids Dicationic ionic liquids Solubility Cytotoxicity Drug delivery Bioavailability |
| title | Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs |
| title_full | Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs |
| title_fullStr | Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs |
| title_full_unstemmed | Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs |
| title_short | Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs |
| title_sort | using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water soluble drugs |
| topic | Dicationic ionic liquids Solubility Cytotoxicity Drug delivery Bioavailability |
| url | http://www.sciencedirect.com/science/article/pii/S2772422023000046 |
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