68
tested, 2 gave acceptable solubility: D-(+)-glucose:sucrose 1:1 and maleic
acid:choline chloride 1:3. Hydrolysis of curcumin was also reduced in these solvents. The phototoxicity of these formulations toward bacteria is discussed in the
section on the antimicrobial activity of deep eutectic solvents. They then turned
their attention to an anionic porphyrin, meso-tetra-(4-carboxyphenyl)-porphine
(TCPP) (Wikene et al. 2016). From absorption and fluorescence spectroscopy,
meso-tetra-(4-carboxyphenyl)-porphine was found to be soluble in a dicationic
form in acidic deep eutectic solvents formed from citric acid:sucrose 1:1, DL-malic
acid:D-fructose:D-glucose 1:1:1, and choline chloride:xylitol 5:2. Phototoxicity
was observed toward several bacterial species (see below).
The same group also investigated a neutral porphyrin, meso-tetra(4hydroxyphenyl)porphine (THPP) (Wikene et al. 2015b). Two natural deep eutectic
solvents were selected for their ability to increase the solubility and stability: citric
acid:sucrose 1:1 and D-glucose:DL-malic acid 1:1. They were able to show
increased phototoxicity toward Enterococcus faecalis and Escherichia coli compared with phosphate-buffered saline. A follow-up study (Wikene et al. 2017)
extended these observations to four bacterial and one fungal species. In 2016, a
patent was filed entitled “Eutectic solvents and uses thereof,” describing the use of
deep eutectic solvents and natural deep eutectic solvents for bacterial killing by
photodynamic therapy (Tønnesen and Wikene 2016).
Antimicrobial Drugs
Other patent applications, filed by Zakrewsky et al. claim that a wide range of drugs
can be incorporated into deep eutectic solvents to improve their transdermal penetration, with treatment of skin infections as a particular example (see below)
(Zakrewsky et al. 2015; Zakrewsky et al. 2016b).
Several more specific reports have described the solubilization of antimicrobial
molecules in deep eutectic solvents. Olivares et al. have formulated two β-lactam
antibiotics, clavulanic acid and imipenem, in the composition of betaine and urea in
a molar ratio of 1:1.5 (Olivares et al. 2018). They used spectroscopic techniques
(infrared (IR) and nuclear magnetic resonance) to characterize the deep eutectic
solvents, with the results highlighting the importance of hydrogen bonds in their
microstructure and the disruption of this structure by addition of water. Both the
chemical stability and the antimicrobial activity of the two antibiotics were increased
severalfolds by incorporation into the solvents compared with an aqueous solution.
The solubility of antofloxacin hydrochloride, an antibiotic in the fluoroquinolone
family, was found to be increased in a deep eutectic solvent composed of choline
chloride:para-toluenesulfonic acid 1:2 compared with ethanol:water and
ethanol:acetonitrile mixtures (Zhang et al. 2019).
Two other antibacterial molecules – sulfanilamide and sulfacetamide – were
solubilized in natural deep eutectic solvents based on choline chloride paired with
C.-H. Nguyen et al.
tested, 2 gave acceptable solubility: D-(+)-glucose:sucrose 1:1 and maleic
acid:choline chloride 1:3. Hydrolysis of curcumin was also reduced in these solvents. The phototoxicity of these formulations toward bacteria is discussed in the
section on the antimicrobial activity of deep eutectic solvents. They then turned
their attention to an anionic porphyrin, meso-tetra-(4-carboxyphenyl)-porphine
(TCPP) (Wikene et al. 2016). From absorption and fluorescence spectroscopy,
meso-tetra-(4-carboxyphenyl)-porphine was found to be soluble in a dicationic
form in acidic deep eutectic solvents formed from citric acid:sucrose 1:1, DL-malic
acid:D-fructose:D-glucose 1:1:1, and choline chloride:xylitol 5:2. Phototoxicity
was observed toward several bacterial species (see below).
The same group also investigated a neutral porphyrin, meso-tetra(4hydroxyphenyl)porphine (THPP) (Wikene et al. 2015b). Two natural deep eutectic
solvents were selected for their ability to increase the solubility and stability: citric
acid:sucrose 1:1 and D-glucose:DL-malic acid 1:1. They were able to show
increased phototoxicity toward Enterococcus faecalis and Escherichia coli compared with phosphate-buffered saline. A follow-up study (Wikene et al. 2017)
extended these observations to four bacterial and one fungal species. In 2016, a
patent was filed entitled “Eutectic solvents and uses thereof,” describing the use of
deep eutectic solvents and natural deep eutectic solvents for bacterial killing by
photodynamic therapy (Tønnesen and Wikene 2016).
Antimicrobial Drugs
Other patent applications, filed by Zakrewsky et al. claim that a wide range of drugs
can be incorporated into deep eutectic solvents to improve their transdermal penetration, with treatment of skin infections as a particular example (see below)
(Zakrewsky et al. 2015; Zakrewsky et al. 2016b).
Several more specific reports have described the solubilization of antimicrobial
molecules in deep eutectic solvents. Olivares et al. have formulated two β-lactam
antibiotics, clavulanic acid and imipenem, in the composition of betaine and urea in
a molar ratio of 1:1.5 (Olivares et al. 2018). They used spectroscopic techniques
(infrared (IR) and nuclear magnetic resonance) to characterize the deep eutectic
solvents, with the results highlighting the importance of hydrogen bonds in their
microstructure and the disruption of this structure by addition of water. Both the
chemical stability and the antimicrobial activity of the two antibiotics were increased
severalfolds by incorporation into the solvents compared with an aqueous solution.
The solubility of antofloxacin hydrochloride, an antibiotic in the fluoroquinolone
family, was found to be increased in a deep eutectic solvent composed of choline
chloride:para-toluenesulfonic acid 1:2 compared with ethanol:water and
ethanol:acetonitrile mixtures (Zhang et al. 2019).
Two other antibacterial molecules – sulfanilamide and sulfacetamide – were
solubilized in natural deep eutectic solvents based on choline chloride paired with
C.-H. Nguyen et al.