67
but also by the antioxidant capacity. The toxicity of the deep eutectic solvents determined in vitro toward two human tumor cell lines was low, while the antiproliferative activity of the choline chloride:malic acid extract was much higher than that of
a traditional methanolic extract.
In a work designed to evaluate the antioxidant capacity of a number of phenolic
compounds, Durand et al. used a natural deep eutectic solvent consisting of
1,2- propanediol (propylene glycol), choline chloride, and water in equimolar proportions as a vehicle to add the active molecules to cultured fibroblasts (Durand
et al. 2017). For compounds with low water solubility, this provided a better method
for obtaining dose-response curves than ethanol or dimethyl sulfoxide. The same
group used this natural deep eutectic solvent to formulate resveratrol and test its
ability to inhibit the enzyme matrix metalloprotease-9 in cultures of activated macrophages, thereby avoiding the toxicity associated with dissolving the molecule in
dimethyl sulfoxide (Shamseddin et al. 2017).
Flavonoids are another class of antioxidant products for which deep eutectic solvents can bring considerable advantages in extraction and solubilization. To this
end, Tang et al. made a detailed study of the solubility of three plant-derived flavonoids: phloretin, phlorizin, and naringin dihydrochalcone (naringin DC) in natural
deep eutectic solvents that combined citric acid, choline chloride, glucose, and
sucrose in various combinations with water (Tang et al. 2016). The density and
viscosity of the solvents were measured, and the solubility parameters were
analyzed. As observed in many studies, solubility in the natural deep eutectic
solvents increased with increasing temperature. Taking all the factors into
consideration, the best solvents for the extraction and solubilization of flavonoids
were reported to be citric acid:glucose:water 1:1:12 and choline chloride:citric
acid:water 1:1:11.
The solubility of nobiletin, a glucose-lowering flavonoid, was enhanced 450
times compared with water in the so-called “CAGE” solvent consisting of geranic
acid and choline in a 2:1 molar ratio. Nucleic magnetic resonance studies showed
overlapping spectra, suggesting that the flavonoid might be able to act as a hydrogen
bond acceptor within the solvent (Hattori et al. 2019).
Photosensitizers
Photosensitizing compounds have great potential for the treatment of both infections and cancer but are generally hydrophobic and thus difficult to administer.
Photodynamic therapy (PDT) consists of first giving the photosensitizer which
accumulates, with variable degrees of specificity, in the target (bacteria or tumor
cell). On illumination, the photosensitizer produces reactive oxygen species that
destroy the target. It is clear that the success of this therapy depends on fast and
accurate accumulation of the photosensitizer in the target. A group at the University
of Oslo has been studying the use of natural deep eutectic solvents as solvents for
agent used in antimicrobial photodynamic therapy. They first evaluated a panel of
solvents for a natural compound, curcumin (Wikene et al. 2015a). Of 17 solvents
2 Deep Eutectic Solvents for Innovative Pharmaceutical Formulations
but also by the antioxidant capacity. The toxicity of the deep eutectic solvents determined in vitro toward two human tumor cell lines was low, while the antiproliferative activity of the choline chloride:malic acid extract was much higher than that of
a traditional methanolic extract.
In a work designed to evaluate the antioxidant capacity of a number of phenolic
compounds, Durand et al. used a natural deep eutectic solvent consisting of
1,2- propanediol (propylene glycol), choline chloride, and water in equimolar proportions as a vehicle to add the active molecules to cultured fibroblasts (Durand
et al. 2017). For compounds with low water solubility, this provided a better method
for obtaining dose-response curves than ethanol or dimethyl sulfoxide. The same
group used this natural deep eutectic solvent to formulate resveratrol and test its
ability to inhibit the enzyme matrix metalloprotease-9 in cultures of activated macrophages, thereby avoiding the toxicity associated with dissolving the molecule in
dimethyl sulfoxide (Shamseddin et al. 2017).
Flavonoids are another class of antioxidant products for which deep eutectic solvents can bring considerable advantages in extraction and solubilization. To this
end, Tang et al. made a detailed study of the solubility of three plant-derived flavonoids: phloretin, phlorizin, and naringin dihydrochalcone (naringin DC) in natural
deep eutectic solvents that combined citric acid, choline chloride, glucose, and
sucrose in various combinations with water (Tang et al. 2016). The density and
viscosity of the solvents were measured, and the solubility parameters were
analyzed. As observed in many studies, solubility in the natural deep eutectic
solvents increased with increasing temperature. Taking all the factors into
consideration, the best solvents for the extraction and solubilization of flavonoids
were reported to be citric acid:glucose:water 1:1:12 and choline chloride:citric
acid:water 1:1:11.
The solubility of nobiletin, a glucose-lowering flavonoid, was enhanced 450
times compared with water in the so-called “CAGE” solvent consisting of geranic
acid and choline in a 2:1 molar ratio. Nucleic magnetic resonance studies showed
overlapping spectra, suggesting that the flavonoid might be able to act as a hydrogen
bond acceptor within the solvent (Hattori et al. 2019).
Photosensitizers
Photosensitizing compounds have great potential for the treatment of both infections and cancer but are generally hydrophobic and thus difficult to administer.
Photodynamic therapy (PDT) consists of first giving the photosensitizer which
accumulates, with variable degrees of specificity, in the target (bacteria or tumor
cell). On illumination, the photosensitizer produces reactive oxygen species that
destroy the target. It is clear that the success of this therapy depends on fast and
accurate accumulation of the photosensitizer in the target. A group at the University
of Oslo has been studying the use of natural deep eutectic solvents as solvents for
agent used in antimicrobial photodynamic therapy. They first evaluated a panel of
solvents for a natural compound, curcumin (Wikene et al. 2015a). Of 17 solvents
2 Deep Eutectic Solvents for Innovative Pharmaceutical Formulations