@article {16746,
	title = {Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs},
	volume = {3},
	year = {2023},
	note = {n/a},
	month = {2023},
	pages = {100052},
	abstract = {<p>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{\textendash} 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.</p>
},
	keywords = {Bioavailability, cytotoxicity, Dicationic ionic liquids, Drug delivery, Solubility},
	isbn = {2772-4220},
	url = {https://www.sciencedirect.com/science/article/pii/S2772422023000046},
	author = {Silva, Ana B.P. and Jesus, Ana R. and Agostinho, Daniela A.S. and Esperan{\c c}a, Jos{\'e} M S S and Paiva, Alexandre and Duarte, Ana R.C. and Reis, Patr{\'\i}cia M.}
}
