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antitumor activity itself but present some cytotoxicity. The systems prepared were
myristic acid:limonene (1:1, 1:2, and 2:1), menthol:limonene (1:1, 1:2, and 2:1),
capric acid:limonene (1:1, 1:2, and 2:1), and ibuprofen:limonene (1:1, 1:2, 2:1, 1:4,
and 1:8); all of them present antitumor activity; however, only ibuprofen:limonene
(1:4) was able to inhibit HT29 without compromising cell viability and also improve
the anti-inflammatory activity of ibuprofen (Pereira et al. 2019). The studies of
these therapeutic mixtures in vitro and in vivo are essential for understanding the
mechanisms that govern the therapeutic effect and the possible interactions that
these mixtures have with different cells and tissues. The implementation of these
biological studies accompanied with modeling of the interaction and permeation
through cellular membranes could be very promising and help formulate mixtures
with specific targets and low toxicity.
3.3.2 Biomedical Formulation with Therapeutic Deep
Eutectic Systems
The design and formulation of suitable drug delivery carriers is another major concern of the pharmaceutical industry, and different examples of formulations are
reported in the literature. Tuntarawongsa and Phaechamud have previously prepared
eutectic mixtures with menthol and camphor, borneol, and WS-3 and observe an
increase of drug bioavailability. Later, they incorporate a polymer in the eutectic
mixture menthol and camphor to prolong the drug release and have a slow drug diffusion. The polymeric eutectic system with Eudragit
®
was used as a vehicle for
ibuprofen, due to its higher solubility in the system menthol:camphor, and the
hydrophobic part turns this mixture suitable for controlled release of ibuprofen, for
example, in periodontitis (Tuntarawongsa and Phaechamud (2012); Mbous et al.
2017a, b). Mano et al. prepared THEDES with choline chloride and mandelic acid
(1:2) which were encapsulated in gelatin fibers by electrospinning, producing fibers
with a smooth surface and that can adopt many conformations. These fibers were
designed to obtain fast-dissolving delivery systems (FDDS) with simple techniques
(Mano et al. 2016; Roda et al. 2019).
Zainal-Abidin et al. explored the use of DES to functionalize the surface of nanodrug carriers of graphene. In spite of these, nanodrug carriers of graphene per se
represent an alternative way for increasing the efficiency of drug delivery, due to
their high surface area, intrinsic mobility, thermal stability, and high loading capacity. But these nanocarriers of graphene could present some toxicity for humans and
for the environment, and the functionalization of these carriers with DES allows
surface modifications and introduction of functional groups that increase the biocompatibility of graphene (Zainal-Abidin et al. 2019).
In order to observe an improvement of the characteristics of a drug in an eutectic
mixture, Patel et al. studied the eutectic mixture nimesulide:nicotinamide (1:2) and
produce a powder through spray dried and verify that the solubility of this mixture
was enhanced 14-fold and the dissolution in water enhanced 2-fold, when compared
F. Santos and A. R. C. Duarte
antitumor activity itself but present some cytotoxicity. The systems prepared were
myristic acid:limonene (1:1, 1:2, and 2:1), menthol:limonene (1:1, 1:2, and 2:1),
capric acid:limonene (1:1, 1:2, and 2:1), and ibuprofen:limonene (1:1, 1:2, 2:1, 1:4,
and 1:8); all of them present antitumor activity; however, only ibuprofen:limonene
(1:4) was able to inhibit HT29 without compromising cell viability and also improve
the anti-inflammatory activity of ibuprofen (Pereira et al. 2019). The studies of
these therapeutic mixtures in vitro and in vivo are essential for understanding the
mechanisms that govern the therapeutic effect and the possible interactions that
these mixtures have with different cells and tissues. The implementation of these
biological studies accompanied with modeling of the interaction and permeation
through cellular membranes could be very promising and help formulate mixtures
with specific targets and low toxicity.
3.3.2 Biomedical Formulation with Therapeutic Deep
Eutectic Systems
The design and formulation of suitable drug delivery carriers is another major concern of the pharmaceutical industry, and different examples of formulations are
reported in the literature. Tuntarawongsa and Phaechamud have previously prepared
eutectic mixtures with menthol and camphor, borneol, and WS-3 and observe an
increase of drug bioavailability. Later, they incorporate a polymer in the eutectic
mixture menthol and camphor to prolong the drug release and have a slow drug diffusion. The polymeric eutectic system with Eudragit
®
was used as a vehicle for
ibuprofen, due to its higher solubility in the system menthol:camphor, and the
hydrophobic part turns this mixture suitable for controlled release of ibuprofen, for
example, in periodontitis (Tuntarawongsa and Phaechamud (2012); Mbous et al.
2017a, b). Mano et al. prepared THEDES with choline chloride and mandelic acid
(1:2) which were encapsulated in gelatin fibers by electrospinning, producing fibers
with a smooth surface and that can adopt many conformations. These fibers were
designed to obtain fast-dissolving delivery systems (FDDS) with simple techniques
(Mano et al. 2016; Roda et al. 2019).
Zainal-Abidin et al. explored the use of DES to functionalize the surface of nanodrug carriers of graphene. In spite of these, nanodrug carriers of graphene per se
represent an alternative way for increasing the efficiency of drug delivery, due to
their high surface area, intrinsic mobility, thermal stability, and high loading capacity. But these nanocarriers of graphene could present some toxicity for humans and
for the environment, and the functionalization of these carriers with DES allows
surface modifications and introduction of functional groups that increase the biocompatibility of graphene (Zainal-Abidin et al. 2019).
In order to observe an improvement of the characteristics of a drug in an eutectic
mixture, Patel et al. studied the eutectic mixture nimesulide:nicotinamide (1:2) and
produce a powder through spray dried and verify that the solubility of this mixture
was enhanced 14-fold and the dissolution in water enhanced 2-fold, when compared
F. Santos and A. R. C. Duarte