Future Journal of Pharmaceutical Sciences,
Год журнала:
2024,
Номер
10(1)
Опубликована: Ноя. 20, 2024
Abstract
Background
Lung
cancer
remains
a
leading
type,
but
current
chemotherapy
is
limited
by
issues
including
poor
drug
delivery,
toxicity,
and
resistance.
To
address
these
challenges,
we
developed
novel
PLGA-PEG-LHRH
(PPL)
nanoconjugate
system
for
improved
delivery.
Curcumin,
known
its
anticancer
P-gp
inhibition
properties,
was
co-loaded
with
bcl2siRNA
(bclsR)
to
inhibit
the
bcl2
protein,
thus
overcoming
both
resistance
mechanisms.
Results
The
PPL
conjugate
successfully
synthesized
characterized
using
FTIR,
1
H
NMR,
XRD,
XPS
BCA
assay.
Curcumin
bclsR-loaded
PLGA
nanoemulsions
were
prepared
double
emulsion
solvent
evaporation
method
characterized.
optimized
had
size
of
179
±
16
nm,
favorable
zeta
potential,
high
entrapment,
confirmed
via
TEM.
Controlled
release
studies
indicated
83%
within
24
h.
In
vitro
revealed
significant
cytotoxicity
against
A549
lung
cells,
showing
IC50
8.24
µg/mL
compared
21.26
plain
curcumin.
Enhanced
cellular
uptake
effective
targeting
cells
observed.
Molecular
analyses
demonstrated
downregulation
MDR1
Bcl2
RNA
protein
expression,
highlighting
nanoconjugates'
ability
suppress
Pharmacokinetic
in
Wistar
rats
showed
superior
plasma
concentrations,
half-life,
AUC
versus
pure
suspension.
Biodistribution
increased
accumulation
lungs.
vivo
efficacy
Balb/c
mice
higher
tumor
ratios
CUR-siRNA
NPs
(66.89%)
CUR-PPL
(59.84%)
which
further
TNFα
p53
levels
blood.
Histopathological
good
healing
NP-
NP-treated
Conclusion
From
study,
it
may
be
concluded
that
system,
loaded
curcumin
bcsR,
can
potentially
effective,
multifunctional
targeted
approach
therapy.
Graphical
Pharmaceutical Development and Technology,
Год журнала:
2024,
Номер
30(1), С. 37 - 56
Опубликована: Дек. 27, 2024
This
study
aims
to
develop
a
thermoresponsive
biomaterial
system
of
irinotecan
(IRT)
and
curcumin
(CUR)
nano-transferosomal
gel
(IRT-CUR-NTG)
for
targeting
colorectal
cancer
(CRC).
The
IRT-CUR-NTs
were
statistically
optimized
loaded
into
poloxamer-based
thermosensitive
gel.
Transmission
electron
microscopy
(TEM),
Differential
scanning
calorimetry
(DSC)
Fourier-transform
infrared
spectroscopy
(FTIR)
the
performed,
whereas
pH,
gelation
time,
temperature,
mucoadhesive
strength
IRT-CUR-NTG
investigated.
In-vitro
release
anticancer
analyses
explored
using
HT29
cells.
Additionally,
in-vivo
pharmacokinetics
was
investigated
followed
by
histopathological
examination
analysis.
PS,
PDI,
ZP,
%EE
IRT
CUR
found
be
136.15
nm,
0.143,
-15.5
mV,
95.05%
85.12%,
respectively.
exhibited
spherical
shape
with
no
chemical
interactions
among
constituents.
Similarly,
homogenous
suitable
rectal
administration.
manifested
prolonged
profiles
CUR.
Moreover,
significantly
enhanced
(4-fold)
bioavailability
toxicity
observed
when
compared
conventional
more
effective
against
cell
lines.
In-vivo
antitumor
analysis
demonstrated
reduced
tumor
volume
mass
after
treatment
IRT-CUT-NTG,
indicating
improved
effect.
It
can
concluded
that
is
cancer.
Future Journal of Pharmaceutical Sciences,
Год журнала:
2024,
Номер
10(1)
Опубликована: Ноя. 20, 2024
Abstract
Background
Lung
cancer
remains
a
leading
type,
but
current
chemotherapy
is
limited
by
issues
including
poor
drug
delivery,
toxicity,
and
resistance.
To
address
these
challenges,
we
developed
novel
PLGA-PEG-LHRH
(PPL)
nanoconjugate
system
for
improved
delivery.
Curcumin,
known
its
anticancer
P-gp
inhibition
properties,
was
co-loaded
with
bcl2siRNA
(bclsR)
to
inhibit
the
bcl2
protein,
thus
overcoming
both
resistance
mechanisms.
Results
The
PPL
conjugate
successfully
synthesized
characterized
using
FTIR,
1
H
NMR,
XRD,
XPS
BCA
assay.
Curcumin
bclsR-loaded
PLGA
nanoemulsions
were
prepared
double
emulsion
solvent
evaporation
method
characterized.
optimized
had
size
of
179
±
16
nm,
favorable
zeta
potential,
high
entrapment,
confirmed
via
TEM.
Controlled
release
studies
indicated
83%
within
24
h.
In
vitro
revealed
significant
cytotoxicity
against
A549
lung
cells,
showing
IC50
8.24
µg/mL
compared
21.26
plain
curcumin.
Enhanced
cellular
uptake
effective
targeting
cells
observed.
Molecular
analyses
demonstrated
downregulation
MDR1
Bcl2
RNA
protein
expression,
highlighting
nanoconjugates'
ability
suppress
Pharmacokinetic
in
Wistar
rats
showed
superior
plasma
concentrations,
half-life,
AUC
versus
pure
suspension.
Biodistribution
increased
accumulation
lungs.
vivo
efficacy
Balb/c
mice
higher
tumor
ratios
CUR-siRNA
NPs
(66.89%)
CUR-PPL
(59.84%)
which
further
TNFα
p53
levels
blood.
Histopathological
good
healing
NP-
NP-treated
Conclusion
From
study,
it
may
be
concluded
that
system,
loaded
curcumin
bcsR,
can
potentially
effective,
multifunctional
targeted
approach
therapy.
Graphical