PubMed,
Год журнала:
2023,
Номер
13(10), С. 4623 - 4643
Опубликована: Янв. 1, 2023
Methotrexate
(MTX)
which
is
one
of
the
longest-used
cytostatics,
belongs
to
group
antimetabolites
and
used
for
treatment
in
different
types
cancer
as
well
during
autoimmune
diseases.
MTX
can
act
a
modulator
enable
create
optimal
environment
generate
specific
anti-tumor
immune
response.
A
novel
system
delivery
its
conjugation
with
high-molecular-weight
carriers
such
hydroxyethyl
starch
(HES),
modified
amylopectin-based
polymer
applied
medicine
colloidal
plasma
volume
expander.
Such
modification
prolongs
half-life
HES-MTX
nanoconjugate
improves
distribution
drug
body.
In
current
study,
we
focused
on
evaluating
dose-dependent
therapeutic
efficacy
chemotherapy
compared
free
form
MTX,
examining
time-dependent
changes
local
systemic
response
induced
by
this
therapy.
To
confirm
higher
effectiveness
comparison
analyzed
action
using
murine
MC38
colon
carcinoma
B16
F0
melanoma
tumor
models.
It
was
noted
that
at
dose
20
mg/kg
b.w.
more
effective
growth
inhibition
than
both
One
main
differences
between
two
models
concerned
kinetics
appearance
immunomodulation.
tumors,
beneficial
change
microenvironment
(TME)
landscape,
manifested
depletion
pro-tumor
cells,
increased
influx
cells
strong
activity
already
3
days
after
administration,
while
model,
these
occurred
10
start
Thus,
immunomodulatory
potential
may
be
closely
related
cell
composition
TME,
combined
additional
immunotherapies,
would
enhance
nanoconjugate.
Cuproptosis-based
cancer
nanomedicine
has
received
widespread
attention
recently.
However,
cuproptosis
against
pancreatic
ductal
adenocarcinoma
(PDAC)
is
severely
limited
by
stem
cells
(CSCs),
which
reside
in
the
hypoxic
stroma
and
adopt
glycolysis
metabolism
accordingly
to
resist
cuproptosis-induced
mitochondria
damage.
Here,
we
leverage
hyperbaric
oxygen
(HBO)
regulate
CSC
overcoming
tumor
hypoxia
augment
elimination
efficacy
of
polydopamine
hydroxyethyl
starch
stabilized
copper-diethyldithiocarbamate
nanoparticles
(CuET@PH
NPs).
Mechanistically,
while
HBO
CuET@PH
NPs
inhibit
oxidative
phosphorylation,
respectively,
combination
potently
suppresses
energy
CSCs,
thereby
achieving
robust
inhibition
PDAC
elongating
mice
survival
importantly.
This
study
reveals
novel
insights
into
effects
on
suggests
that
with
holds
significant
clinical
translation
potential
for
patients.
International Journal of Nanomedicine,
Год журнала:
2024,
Номер
Volume 19, С. 5139 - 5156
Опубликована: Июнь 1, 2024
Introduction:
Although
flavonoid
compounds
exhibit
various
pharmacological
activities,
their
clinical
applications
are
restricted
by
low
oral
bioavailability
owing
to
poor
solubility.
Nanocrystals
(NCs)
represent
an
excellent
strategy
for
enhancing
the
of
flavonoids.
Hydroxyethyl
starch
(HES),
a
biomaterial
compound
used
as
plasma
expander,
could
be
ideal
stabilizer
material
preparing
NCs.
Methods:
HES
was
stabilize
nanocrystals
(NCs),
using
luteolin
(LUT)
model
drug.
After
full
characterization,
freeze-drying
and
storage
stability,
solubility,
intestinal
absorption,
pharmacokinetics,
in
vivo
anti-hyperuricemic
effect
optimized
HES-stabilized
LUT
NCs
(LUT-HES
NCs)
were
investigated.
Results:
Uniformed
LUT-HES
prepared
with
mean
particle
size
191.1±
16.8
nm,
zeta
potential
about
−
23
mV,
drug
encapsulation
efficiency
98.52
±
1.01%,
loading
49.26
0.50%.
The
freeze-dried
powder
showed
good
re-dispersibility
stability
9
months.
Notably,
compared
coarse
drug,
exhibited
improved
saturation
solubility
(7.49
times),
increased
dissolution
rate,
enhanced
Caco-2
cellular
uptake
(2.78
times)
(Fr=355.7%).
Pharmacodynamic
studies
that
remarkably
lowered
serum
uric
acid
levels
69.93%
ameliorated
renal
damage
hyperuricemic
mice.
Conclusion:
is
poorly
soluble
provides
promising
application
these
compounds.
may
alternative
or
complementary
hyperuricemia
treatment.
Keywords:
starch,
nanocrystals,
stabilizer,
luteolin,
bioavailability,
anti-hyperuricemia
