Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs

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

doi:10.1016/j.jil.2023.100052

Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs

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

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

66 Downloads (Pure)

Abstract

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.

Original language	English
Article number	100052
Number of pages	9
Journal	Journal of Ionic Liquids
Volume	3
Issue number	1
DOIs	https://doi.org/10.1016/j.jil.2023.100052
Publication status	Published - Jun 2023

Keywords

Bioavailability
Cytotoxicity
Dicationic ionic liquids
Drug delivery
Solubility

Access to Document

10.1016/j.jil.2023.100052Licence: CC BY

Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water solubles drugsFinal published version, 2.08 MBLicence: CC BY

Cite this

@article{67a4dd144f8942d28abc2ab155b4b309,

title = "Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs",

abstract = "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.",

keywords = "Bioavailability, Cytotoxicity, Dicationic ionic liquids, Drug delivery, Solubility",

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 Alexandre Paiva and Duarte, {Ana R.C.} and Reis, {Patr{\'i}cia M.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = jun,

doi = "10.1016/j.jil.2023.100052",

language = "English",

volume = "3",

journal = "Journal of Ionic Liquids",

issn = "2772-4220",

publisher = "Elsevier Science Publisher B.V.",

number = "1",

}

TY - JOUR

T1 - Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs

AU - Silva, Ana B.P.

AU - Jesus, Ana R.

AU - Agostinho, Daniela A.S.

AU - Esperança, José M.S.S.

AU - Paiva, Alexandre

AU - Duarte, Ana R.C.

AU - Reis, Patrícia M.

PY - 2023/6

Y1 - 2023/6

N2 - 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.

AB - 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.

KW - Bioavailability

KW - Cytotoxicity

KW - Dicationic ionic liquids

KW - Drug delivery

KW - Solubility

UR - http://www.scopus.com/inward/record.url?scp=85165802335&partnerID=8YFLogxK

U2 - 10.1016/j.jil.2023.100052

DO - 10.1016/j.jil.2023.100052

M3 - Article

AN - SCOPUS:85165802335

SN - 2772-4220

VL - 3

JO - Journal of Ionic Liquids

JF - Journal of Ionic Liquids

IS - 1

M1 - 100052

ER -

Using dicationic ionic liquids to upgrade the cytotoxicity and solubility of poorly water-soluble drugs

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this