71
2.3.2 Solubilization and Stabilization
of High- Molecular-Weight Molecules
As well as their applications for formulation of small molecules, deep eutectic solvents have also been found to be good solvents for biological macromolecules. As
early as 2011, Choi et al. observed good solubility of salmon deoxyribonucleic acid
(DNA), albumin, amylase, and starch in some natural deep eutectic solvents (Choi
et al. 2011).
In their 2013 study, Dai et al. included three high-molecular-weight natural products: gluten (a plant protein), deoxyribonucleic acid, and starch (Dai et al. 2013).
For each of these compounds, a deep eutectic solvent composition was found that
could increase their solubility compared with water. For starch, which is not soluble
in pure water even at 100 °C, 7.55 g/mole solvent were detected in glucose:choline
chloride:water 2:5:5 at this temperature. The solubilities of both gluten and deoxyribonucleic acid were both increased in a solvent consisting of lactic acid, glucose,
and water in a 5:1:3 molar ratio by factors of 88 and 34, respectively. Recently,
Haraźna et al. showed a good solubility of lignin, a biopolymer from wood, in a
solvent formed from choline chloride and a mixture of bacterially derived organic
acids (Haraźna et al. 2019).
Table 3 gives a summary of the applications of deep eutectic solvents to biomacromolecules. Some more detailed results for several classes of macromolecule are
given below.
Cage Molecules
Cyclodextrins and curcurbit[n]urils are smaller macromolecules that have the particularity of being cyclic cage molecules that can complex a wide range of guest
molecules. As such, they have a number of applications in the pharmaceutical and
food industries, but their water solubility can be limiting, especially for
curcurbit[n]urils and β- and some substituted cyclodextrins. In a patent application
filed by Fourmentin et al. in 2016 and published in 2018 (Fourmentin et al. 2018),
it was reported that cyclodextrins could be dissolved in deep eutectic solvents composed of choline chloride and urea. In follow-up studies (Moufawad et al. 2019), the
dissolution process of cyclodextrins in this deep eutectic solvent was described in
detail, and it was shown that the ability of the cyclodextrin to form inclusion complexes with methyl orange was retained. Furthermore, the effect of adding water to
the system was studied, and a complex formed between β-cyclodextrin and piroxicam in the deep eutectic solvent was characterized by nuclear magnetic resonance
(NMR) (Colombo Dugoni et al. 2019). More recently, El Achkar et al. have demonstrated the possibility of preparing a low melting mixture composed of levunilic
acid and a cyclodextrin: the randomly methylated β-cyclodextrin that is able to
include trans-anethole (Achkar et al. 2020).
2 Deep Eutectic Solvents for Innovative Pharmaceutical Formulations
2.3.2 Solubilization and Stabilization
of High- Molecular-Weight Molecules
As well as their applications for formulation of small molecules, deep eutectic solvents have also been found to be good solvents for biological macromolecules. As
early as 2011, Choi et al. observed good solubility of salmon deoxyribonucleic acid
(DNA), albumin, amylase, and starch in some natural deep eutectic solvents (Choi
et al. 2011).
In their 2013 study, Dai et al. included three high-molecular-weight natural products: gluten (a plant protein), deoxyribonucleic acid, and starch (Dai et al. 2013).
For each of these compounds, a deep eutectic solvent composition was found that
could increase their solubility compared with water. For starch, which is not soluble
in pure water even at 100 °C, 7.55 g/mole solvent were detected in glucose:choline
chloride:water 2:5:5 at this temperature. The solubilities of both gluten and deoxyribonucleic acid were both increased in a solvent consisting of lactic acid, glucose,
and water in a 5:1:3 molar ratio by factors of 88 and 34, respectively. Recently,
Haraźna et al. showed a good solubility of lignin, a biopolymer from wood, in a
solvent formed from choline chloride and a mixture of bacterially derived organic
acids (Haraźna et al. 2019).
Table 3 gives a summary of the applications of deep eutectic solvents to biomacromolecules. Some more detailed results for several classes of macromolecule are
given below.
Cage Molecules
Cyclodextrins and curcurbit[n]urils are smaller macromolecules that have the particularity of being cyclic cage molecules that can complex a wide range of guest
molecules. As such, they have a number of applications in the pharmaceutical and
food industries, but their water solubility can be limiting, especially for
curcurbit[n]urils and β- and some substituted cyclodextrins. In a patent application
filed by Fourmentin et al. in 2016 and published in 2018 (Fourmentin et al. 2018),
it was reported that cyclodextrins could be dissolved in deep eutectic solvents composed of choline chloride and urea. In follow-up studies (Moufawad et al. 2019), the
dissolution process of cyclodextrins in this deep eutectic solvent was described in
detail, and it was shown that the ability of the cyclodextrin to form inclusion complexes with methyl orange was retained. Furthermore, the effect of adding water to
the system was studied, and a complex formed between β-cyclodextrin and piroxicam in the deep eutectic solvent was characterized by nuclear magnetic resonance
(NMR) (Colombo Dugoni et al. 2019). More recently, El Achkar et al. have demonstrated the possibility of preparing a low melting mixture composed of levunilic
acid and a cyclodextrin: the randomly methylated β-cyclodextrin that is able to
include trans-anethole (Achkar et al. 2020).
2 Deep Eutectic Solvents for Innovative Pharmaceutical Formulations