45
As far as rheology is concerned, viscosity can be an issue for deep eutectic solvents (Moura et al. 2017). On one hand, for topical applications, a more viscous
preparation would be an advantage as long as it can be easily spread on the skin. On
the other hand, for other routes, excessive viscosity would hamper administration by
other routes, such as oral, and can be a cause of toxicity.
2.2 Toxicity of Deep Eutectic Solvents
For any new pharmaceutical ingredient, toxicity profiling is extremely important.
Many of the studies described above included an assessment of the effect of the deep
eutectic solvents on mammalian tissues. A few systematic studies of toxicity have
been made. Since deep eutectic solvents are proposed as “green solvents,” emphasis
has often been placed on their toxicity to the environment, and in particular, aquatic
organisms have often been used as indicators. The studies that have been published
have usually focused on bacterial cells, human cell lines in culture, and in vivo studies in rodents, although other organisms such as fungal cells, plants, invertebrates,
and fish have also figured in the literature.
2.2.1 Toxicity Toward Microorganisms
In 2013, Hayyan et al. first studied the toxicity of deep eutectic solvents toward
bacterial and eukaryotic cells (Hayyan et al. 2013). They chose two Gram-negative
bacteria species (Escherichia coli, Pseudomonas aeruginosa) and two Grampositive ones (Bacillus subtilis, Staphylococcus aureus) as well as brine shrimp
(Artemia saliva) larvae as an indicator of ecotoxicity. They used deep eutectic solvents prepared from choline chloride combined with urea, glycerol, ethylene glycol,
and triethylene glycol. In this study, they observed no inhibition of bacterial growth.
When Mao et al. investigated the toxicity of deep eutectic solvents composed of
choline chloride and urea, ethylene glycol, and glycerol toward Arthrobacter simplex, using growth, metabolic activity, and membrane permeability as the criteria of
toxicity, they observed that the toxicity of the deep eutectic solvents was lower than
that of the individual components (Mao et al. 2018). The ability of the bacteria to
perform biotransformations of steroids was also improved in the deep eutectic
solvents.
Wen et al. attempted to assess deep eutectic solvent toxicity and biodegradability
toward several organisms including a bacterium, Escherichia coli (Wen et al. 2015).
The deep eutectic solvents were composed of choline chloride or choline acetate
with urea, glycerol, acetamide, or ethylene glycol at different molar ratios.
Biodegradability was determined in closed bottles with microorganisms from a
water treatment plant. In their experiments, studied solvents were toxic to bacteria
at concentrations above 75 μM, and they inhibited bacterial growth much more than
2 Deep Eutectic Solvents for Innovative Pharmaceutical Formulations
As far as rheology is concerned, viscosity can be an issue for deep eutectic solvents (Moura et al. 2017). On one hand, for topical applications, a more viscous
preparation would be an advantage as long as it can be easily spread on the skin. On
the other hand, for other routes, excessive viscosity would hamper administration by
other routes, such as oral, and can be a cause of toxicity.
2.2 Toxicity of Deep Eutectic Solvents
For any new pharmaceutical ingredient, toxicity profiling is extremely important.
Many of the studies described above included an assessment of the effect of the deep
eutectic solvents on mammalian tissues. A few systematic studies of toxicity have
been made. Since deep eutectic solvents are proposed as “green solvents,” emphasis
has often been placed on their toxicity to the environment, and in particular, aquatic
organisms have often been used as indicators. The studies that have been published
have usually focused on bacterial cells, human cell lines in culture, and in vivo studies in rodents, although other organisms such as fungal cells, plants, invertebrates,
and fish have also figured in the literature.
2.2.1 Toxicity Toward Microorganisms
In 2013, Hayyan et al. first studied the toxicity of deep eutectic solvents toward
bacterial and eukaryotic cells (Hayyan et al. 2013). They chose two Gram-negative
bacteria species (Escherichia coli, Pseudomonas aeruginosa) and two Grampositive ones (Bacillus subtilis, Staphylococcus aureus) as well as brine shrimp
(Artemia saliva) larvae as an indicator of ecotoxicity. They used deep eutectic solvents prepared from choline chloride combined with urea, glycerol, ethylene glycol,
and triethylene glycol. In this study, they observed no inhibition of bacterial growth.
When Mao et al. investigated the toxicity of deep eutectic solvents composed of
choline chloride and urea, ethylene glycol, and glycerol toward Arthrobacter simplex, using growth, metabolic activity, and membrane permeability as the criteria of
toxicity, they observed that the toxicity of the deep eutectic solvents was lower than
that of the individual components (Mao et al. 2018). The ability of the bacteria to
perform biotransformations of steroids was also improved in the deep eutectic
solvents.
Wen et al. attempted to assess deep eutectic solvent toxicity and biodegradability
toward several organisms including a bacterium, Escherichia coli (Wen et al. 2015).
The deep eutectic solvents were composed of choline chloride or choline acetate
with urea, glycerol, acetamide, or ethylene glycol at different molar ratios.
Biodegradability was determined in closed bottles with microorganisms from a
water treatment plant. In their experiments, studied solvents were toxic to bacteria
at concentrations above 75 μM, and they inhibited bacterial growth much more than
2 Deep Eutectic Solvents for Innovative Pharmaceutical Formulations