Choline-Amino Acid Ionic Liquids as Green Functional Excipients to Enhance Drug Solubility

Caparica, Rita; Júlio, Ana; Baby, André Rolim; Araújo, Maria Eduarda; Fernandes, Ana Sofia; Costa, João Guilherme; Almeida, Tânia Santos de

doi:10.3390/pharmaceutics10040288

Cited by 56 publications

(70 citation statements)

References 47 publications

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“…Both prepared choline-amino acid ILs, [Cho][Phe] and [Cho][Gly], revealed to be viscous at room temperature and their structures were confirmed by 1 H NMR and 13 C NMR and the obtained results are in agreement with the literature [23,34].…”

Section: Synthesis Of Ilssupporting

confidence: 82%

“…These results are in agreement with previously published data performed in the same or different experimental conditions but using different cancer cell lines [18,39,41]. Moreover, with this study, it was possible to demonstrate that in the presence of rutin, 786-O cells are more sensitive to its cytotoxic effects than other previously studied cancer cell lines, namely, hepatoma cells of Rattus novergicus (HTC), human breast cancer cells (MDA-MB-231 and MCF-7), and colon cancer cells (HT29 and Caco-2) [7,9,23,39].…”

Section: Discussionmentioning

confidence: 67%

“…Despite these promising results, rutin has very low solubility in water, 0.2 mg/mL [23], which limits its incorporation in delivery systems and, consequently, its applicability. Recently, a previous study from our group showed that the presence of ionic liquids, at non-toxic concentrations, enhanced the solubility of rutin and its loading into O/W emulsions, thus indicating that these salts may be used as green functional excipients [23].…”

Section: Discussionmentioning

confidence: 99%

“…The solubility studies were performed according to a previously published procedure [23]. Briefly, several saturated solutions of rutin were prepared in triplicate, in water and water:IL mixtures, containing 0.3% of [Cho][Phe] or 0.2% of [Cho][Gly] IL.…”

Section: Solubility Studiesmentioning

confidence: 99%

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Anticancer Activity of Rutin and Its Combination with Ionic Liquids on Renal Cells

et al. 2020

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The renal cell carcinoma (RCC) is the most common type of kidney cancer. Identifying novel and more effective therapies, while minimizing toxicity, continues to be fundamental in curtailing RCC. Rutin, a bioflavonoid widely found in nature, has shown promising anticancer properties, but with limited applicability due to its poor water solubility and pharmacokinetics. Thus, the potential anticancer effects of rutin toward a human renal cancer cell line (786-O), while considering its safety in Vero kidney cells, was assessed, as well as the applicability of ionic liquids (ILs) to improve drug delivery. Rutin (up to 50 µM) did not show relevant cytotoxic effects in Vero cells. However, in 786-O cells, a significant decrease in cell viability was already observed at 50 µM. Moreover, exposure to rutin caused a significant increase in the sub-G1 population of 786-O cells, reinforcing the possible anticancer activity of this biomolecule. Two choline-amino acid ILs, at non-toxic concentrations, enhanced rutin’s solubility/loading while allowing the maintenance of rutin’s anticancer effects. Globally, our findings suggest that rutin may have a beneficial impact against RCC and that its combination with ILs ensures that this poorly soluble drug is successfully incorporated into ILs–nanoparticles hybrid systems, allowing controlled drug delivery.

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Section: Synthesis Of Ilssupporting

confidence: 82%

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Solubility Studiesmentioning

confidence: 99%

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Anticancer Activity of Rutin and Its Combination with Ionic Liquids on Renal Cells

et al. 2020

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“…Cell viability was evaluated by the crystal violet (CV) staining assay. Approximately 5 × 10 3 cells in 200 µL of culture medium per well were plated in 96-well plates and incubated for 24 h. Cells were then exposed to ParvD (0.1-25 µM) for 48 h. The CV assay was carried out according to previously described protocols [22][23][24]. Two or three independent experiments were performed, each comprising four replicate cultures.…”

Section: Cell Viabilitymentioning

confidence: 99%

Anti-Migratory and Pro-Apoptotic Properties of Parvifloron D on Triple-Negative Breast Cancer Cells

et al. 2020

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Medicinal plants are important sources of new bioactive compounds with potential anticancer activity. Parvifloron D (ParvD) is an abietane diterpenoid, isolated in high amounts from Plectranthus ecklonii Benth. Previous reports have suggested potential therapeutic properties for ParvD. ParvD has shown pro-apoptotic and cytotoxic effects in leukemia and melanoma cell lines. However, to the best of our knowledge, there are no studies in triple-negative breast cancer (TNBC) models. TNBC is a breast cancer subtype characterized by an aggressive behavior with poor clinical outcomes and weak overall therapeutic responses to the current treatment options. This work aimed at evaluating the anticancer effect of ParvD in MDA-MB-231 cells, a model of human TNBC. To obtain sufficient amounts of purified ParvD the efficiency of several extraction methods was compared. ParvD (0.1–10 µM) decreased cell viability in a concentration-dependent manner. Treatment with ParvD (5 µM) significantly increased the percentage of apoptotic nuclei and exposure to 3 µM ParvD increased the sub-G1 population. Since altered cell adherence, migration, and invasion are determinant processes for the formation of metastases, the effect of ParvD on these cellular processes was tested. Although treatment with ParvD (1 µM) had no effect on cell-substrate attachment, ParvD (1 µM) significantly reduced cell chemotaxis and invasion. This is the first report describing the proapoptotic effect of ParvD in TNBC cells. Moreover, for the first time we have shown that ParvD reduces cell motility, unraveling potential anti-metastatic properties.

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Ligand‐Independent Activation of Aryl Hydrocarbon Receptor and Attenuation of Glutamine Levels by Natural Deep Eutectic Solvent

Denis,

Toledo,

Hakim

et al. 2023

ChemBioChem

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Natural deep eutectic solvents (NADESs) are emerging sustainable alternatives to conventional organic solvents. Beyond their role as laboratory solvents, NADESs are increasingly explored in drug delivery and as therapeutics. Their increasing applications notwithstanding, our understanding of how they interact with biomolecules at multiple levels – metabolome, proteome, and transcriptome – within human cell remain poor. Here, we deploy integrated metabolomics, proteomics, and transcriptomics to probe how NADESs perturb the molecular landscape of human cells. In a human cell line model, we found that an archetypal NADES derived from choline and geranic acid (CAGE) significantly altered the metabolome, proteome, and transcriptome. CAGE upregulated indole‐3‐lactic acid and 4‐hydroxyphenyllactic acid levels, resulting in ligand‐independent activation of aryl hydrocarbon receptor to signal the transcription of genes with implications for inflammation, immunomodulation, cell development, and chemical detoxification. Further, treating the cell line with CAGE downregulated glutamine biosynthesis, a nutrient rapidly proliferating cancer cells require. The ability of CAGE to attenuate glutamine levels is potentially relevant for cancer treatment. These findings suggest that NADESs, even when derived from natural components like choline, can indirectly modulate cell biology at multiple levels, expanding their applications beyond chemistry to biomedicine and biotechnology.

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Choline-Amino Acid Ionic Liquids as Green Functional Excipients to Enhance Drug Solubility

Cited by 56 publications

References 47 publications

Anticancer Activity of Rutin and Its Combination with Ionic Liquids on Renal Cells

Anticancer Activity of Rutin and Its Combination with Ionic Liquids on Renal Cells

Anti-Migratory and Pro-Apoptotic Properties of Parvifloron D on Triple-Negative Breast Cancer Cells

Ligand‐Independent Activation of Aryl Hydrocarbon Receptor and Attenuation of Glutamine Levels by Natural Deep Eutectic Solvent

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