79
phosphate- buffered saline (PBS). This opens up the way to formulations that do not
need a strict cold chain to preserve their activity.
As discussed below, proteins, and in particular insulin, have been included in
deep eutectic solvents in order to improve their cutaneous, oral, or nasal bioavailability (Banerjee et al. 2017; Tanner et al. 2018; Banerjee et al. 2018a; Li et al. 2019).
2.3.3 Antimicrobial Applications
As can be seen from the section on solubilization of small molecules, a number of
antimicrobial agents have been incorporated into deep eutectic solvents. However,
beyond this, it has been observed that some deep eutectic solvents formulations
themselves have antiseptic or antimicrobial activity in their own right, especially by
the topical route. The antimicrobial applications of deep eutectic solvents are summarized in Table 4.
Deep Eutectic Solvents with Intrinsic Antimicrobial Activity
Zakrewsky et al. provide some convincing evidence that a deep eutectic solvent
composed of choline and geranic acid in a 1:2 molar ratio, named CAGE, could act
as an efficient antiseptic agent on the skin (Zakrewsky et al. 2016a). They have
shown antimicrobial activity against a wide range of bacteria, fungi, and viruses,
combined with low skin toxicity. An in vivo study was carried out on a skin infection with Propionibacterium acnes injected intradermally in rat ears. The
choline:geranic acid solvent was much more effective than clindamycin in saline in
reducing ear thickness and reaching bacteria in deeper skin layers. This development of a cheap, effective, and nontoxic topical antimicrobial formulation has considerable importance given the rise of resistance to current agents and the withdrawal
of some compounds because of safety concerns.
This research group has filed several patents with claims concerning the potential
of ionic liquids for use on the skin: their lack of irritability and their ability to transport substances through the skin (Zakrewsky et al. 2015; Zakrewsky et al. 2016b;
Kellar et al. 2018). In particular, the latest patent application (Kellar et al. 2018)
refers to the role of ionic liquids in wound healing as a result of their ability to
inhibit biofilm formation and to control pathogen growth. The “CAGE” formulation
of choline and geranic acid figures prominently in the examples cited. A recent
study has used some physicochemical techniques to probe the mechanism of action
of the choline:geranic acid solvent (Ibsen et al. 2018). Molecular dynamic simulations were used to understand how the “CAGE” components might interact with the
membrane of Escherichia coli. The choline:geranate pair seems to be able to penetrate through the lipopolysaccharide (LPS) layer and bind to the negatively charged
membrane. Membrane disruption could be observed in “CAGE”-treated cells by
scanning electron microscopy. Fourier transform infrared spectroscopy with
2 Deep Eutectic Solvents for Innovative Pharmaceutical Formulations
phosphate- buffered saline (PBS). This opens up the way to formulations that do not
need a strict cold chain to preserve their activity.
As discussed below, proteins, and in particular insulin, have been included in
deep eutectic solvents in order to improve their cutaneous, oral, or nasal bioavailability (Banerjee et al. 2017; Tanner et al. 2018; Banerjee et al. 2018a; Li et al. 2019).
2.3.3 Antimicrobial Applications
As can be seen from the section on solubilization of small molecules, a number of
antimicrobial agents have been incorporated into deep eutectic solvents. However,
beyond this, it has been observed that some deep eutectic solvents formulations
themselves have antiseptic or antimicrobial activity in their own right, especially by
the topical route. The antimicrobial applications of deep eutectic solvents are summarized in Table 4.
Deep Eutectic Solvents with Intrinsic Antimicrobial Activity
Zakrewsky et al. provide some convincing evidence that a deep eutectic solvent
composed of choline and geranic acid in a 1:2 molar ratio, named CAGE, could act
as an efficient antiseptic agent on the skin (Zakrewsky et al. 2016a). They have
shown antimicrobial activity against a wide range of bacteria, fungi, and viruses,
combined with low skin toxicity. An in vivo study was carried out on a skin infection with Propionibacterium acnes injected intradermally in rat ears. The
choline:geranic acid solvent was much more effective than clindamycin in saline in
reducing ear thickness and reaching bacteria in deeper skin layers. This development of a cheap, effective, and nontoxic topical antimicrobial formulation has considerable importance given the rise of resistance to current agents and the withdrawal
of some compounds because of safety concerns.
This research group has filed several patents with claims concerning the potential
of ionic liquids for use on the skin: their lack of irritability and their ability to transport substances through the skin (Zakrewsky et al. 2015; Zakrewsky et al. 2016b;
Kellar et al. 2018). In particular, the latest patent application (Kellar et al. 2018)
refers to the role of ionic liquids in wound healing as a result of their ability to
inhibit biofilm formation and to control pathogen growth. The “CAGE” formulation
of choline and geranic acid figures prominently in the examples cited. A recent
study has used some physicochemical techniques to probe the mechanism of action
of the choline:geranic acid solvent (Ibsen et al. 2018). Molecular dynamic simulations were used to understand how the “CAGE” components might interact with the
membrane of Escherichia coli. The choline:geranate pair seems to be able to penetrate through the lipopolysaccharide (LPS) layer and bind to the negatively charged
membrane. Membrane disruption could be observed in “CAGE”-treated cells by
scanning electron microscopy. Fourier transform infrared spectroscopy with
2 Deep Eutectic Solvents for Innovative Pharmaceutical Formulations