94
second anticancer drug, doxorubicin, was incorporated into the polymer micelles.
Chlorambucil was conjugated with dimethylaminopropanol to form a hydrogen
bond acceptor known as CABAL. This was mixed with 1,4-butanediol in various
ratios to form deep eutectic solvent. A copolymer was synthesized from folic acidmodified β-alanine and poly-ε-caprolactone. When mixed with the optimized deep
eutectic solvent, the polymer formed micelles that could then be loaded with doxorubicin. Drug-loaded micelles were more cytotoxic to the MDA-MB-231 human
breast cancer cell line than to L929 mouse fibroblasts. Finally, tumor volume was
reduced in an in vivo model of rats bearing DMBA-induced mammary tumors when
the animals were treated with doxorubicin-loaded polymer micelles. In a later article, they used a similar formulation to encapsulate paclitaxel (Pradeepkumar et al.
2019a). After an extensive physicochemical characterization, the micelles were
tested for cytotoxicity to HeLa human cervical cancer cells and normal blood cells.
Activity against cancer cells was observed, while there was no toxicity toward the
blood cells.
The same team has also produced a polymer-deep eutectic solvent formulation
using a choline chloride:xylitol deep eutectic solvent as a medium in which to
polymerize 2-hydroxylethyl methacrylate (HEMA) in the form of nanoparticles,
which were then loaded with 5-fluorouracil (Pradeepkumar et al. 2019b). These
nanoparticles were taken up by and showed antiproliferative activity against
HeLa cells.
Florindo et al. have prepared a deep eutectic solvent composed of sodium
dodecanoate and decanoic acid in the form of a hydrogel with rheological properties
suitable for pharmaceutical applications (Florindo et al. 2018).
Deep eutectic solvents also have numerous applications in biotechnology that
could lead to the discovery of new drugs or the preparation of new delivery systems.
The use of deep eutectic solvents to extract natural products has already been
referred to above, for example, the extraction of polyphenols from coffee beans
(Benlebna et al. 2018), antioxidants from grape skin (Radošević et al. 2016), and
flavonoids from plants (Tang et al. 2016). Furthermore, Fu et al. have used a deep
eutectic solvent as a medium for producing a molecularly imprinted polymer in
order to extract β-lactoglobulin (Fu et al. 2019). Also in the section on the
incorporation of high-molecular-weight compounds into deep eutectic solvents, it
has been shown that nanofibers can be produced from lysozyme (Silva et al. 2018a,
b), and a pharmaceutically useful material can be created from gelatin in the
“Glyceline” deep eutectic solvent (Qu et al. 2019).
It has also been demonstrated in work cited above that the activity of many
enzymes can be conserved or even improved in deep eutectic solvents, opening up
the way to their use as alternative media for biotransformations. Thus, the thermal
stability of lysozyme can be increased (Su and Klibanov 2015); the catalytic activity
of catalase (Harifi-Mood et al. 2017), laccase (Khodaverdian et al. 2018), and lipase
(Nascimento et al. 2019) was conserved; and the biotransformation of steroids by
bacteria was efficient (Mao et al. 2018). Finally, Sivapragasam et al. have shown
that some choline-based ionic liquids promoted the growth of the yeast
C.-H. Nguyen et al.
second anticancer drug, doxorubicin, was incorporated into the polymer micelles.
Chlorambucil was conjugated with dimethylaminopropanol to form a hydrogen
bond acceptor known as CABAL. This was mixed with 1,4-butanediol in various
ratios to form deep eutectic solvent. A copolymer was synthesized from folic acidmodified β-alanine and poly-ε-caprolactone. When mixed with the optimized deep
eutectic solvent, the polymer formed micelles that could then be loaded with doxorubicin. Drug-loaded micelles were more cytotoxic to the MDA-MB-231 human
breast cancer cell line than to L929 mouse fibroblasts. Finally, tumor volume was
reduced in an in vivo model of rats bearing DMBA-induced mammary tumors when
the animals were treated with doxorubicin-loaded polymer micelles. In a later article, they used a similar formulation to encapsulate paclitaxel (Pradeepkumar et al.
2019a). After an extensive physicochemical characterization, the micelles were
tested for cytotoxicity to HeLa human cervical cancer cells and normal blood cells.
Activity against cancer cells was observed, while there was no toxicity toward the
blood cells.
The same team has also produced a polymer-deep eutectic solvent formulation
using a choline chloride:xylitol deep eutectic solvent as a medium in which to
polymerize 2-hydroxylethyl methacrylate (HEMA) in the form of nanoparticles,
which were then loaded with 5-fluorouracil (Pradeepkumar et al. 2019b). These
nanoparticles were taken up by and showed antiproliferative activity against
HeLa cells.
Florindo et al. have prepared a deep eutectic solvent composed of sodium
dodecanoate and decanoic acid in the form of a hydrogel with rheological properties
suitable for pharmaceutical applications (Florindo et al. 2018).
Deep eutectic solvents also have numerous applications in biotechnology that
could lead to the discovery of new drugs or the preparation of new delivery systems.
The use of deep eutectic solvents to extract natural products has already been
referred to above, for example, the extraction of polyphenols from coffee beans
(Benlebna et al. 2018), antioxidants from grape skin (Radošević et al. 2016), and
flavonoids from plants (Tang et al. 2016). Furthermore, Fu et al. have used a deep
eutectic solvent as a medium for producing a molecularly imprinted polymer in
order to extract β-lactoglobulin (Fu et al. 2019). Also in the section on the
incorporation of high-molecular-weight compounds into deep eutectic solvents, it
has been shown that nanofibers can be produced from lysozyme (Silva et al. 2018a,
b), and a pharmaceutically useful material can be created from gelatin in the
“Glyceline” deep eutectic solvent (Qu et al. 2019).
It has also been demonstrated in work cited above that the activity of many
enzymes can be conserved or even improved in deep eutectic solvents, opening up
the way to their use as alternative media for biotransformations. Thus, the thermal
stability of lysozyme can be increased (Su and Klibanov 2015); the catalytic activity
of catalase (Harifi-Mood et al. 2017), laccase (Khodaverdian et al. 2018), and lipase
(Nascimento et al. 2019) was conserved; and the biotransformation of steroids by
bacteria was efficient (Mao et al. 2018). Finally, Sivapragasam et al. have shown
that some choline-based ionic liquids promoted the growth of the yeast
C.-H. Nguyen et al.