ACS Nano,
Год журнала:
2024,
Номер
18(52), С. 35310 - 35324
Опубликована: Дек. 16, 2024
The
development
of
effective
oral
drug
delivery
systems
for
targeted
gut-to-liver
transport
remains
a
significant
challenge
due
to
the
multiple
biological
barriers
including
harsh
gastrointestinal
tract
(GIT)
environment
and
complex
protein
corona
(PC)
formation.
In
this
study,
we
developed
ligand-modified
nanoparticles
(NPs)
that
enable
by
crossing
GIT
attenuating
PC
Specifically,
mesoporous
silica
(MSNs)
were
functionalized
with
peptides
targeting
neonatal
Fc
receptor
(FcRn),
capitalizing
on
FcRn
expression
in
small
intestine
liver
delivery.
We
showed
MSNs
decorated
cyclic
binding
peptide
(MSNs-FcBP)
obtained
enhanced
diffusion
intestinal
mucus
superior
transportation
across
compared
unmodified
large
IgG
fragment
(MSNs-Fc),
which
correlated
diminished
adsorption
weaker
interaction
mucin.
After
entering
blood
circulation,
reduced
serum
formation
MSNs-FcBP
reduces
proteolytic
phagocytic
propensity
reticuloendothelial
system,
ultimately
ameliorating
accumulation
hepatocytes.
Pharmacokinetic
pharmacodynamic
studies
diabetic
mice
revealed
effectively
transported
therapeutic
agent
exenatide
epithelium,
leading
hypoglycemic
response
improved
glucose
tolerance.
This
study
underscores
critical
role
ligand
selection
limiting
formation,
thereby
significantly
enhancing
increasing
permeation
minimizing
serum-protein
interactions.
illustrates
potential
strategy
optimize
bioavailability
efficacy.
Journal of Nanobiotechnology,
Год журнала:
2024,
Номер
22(1)
Опубликована: Ноя. 1, 2024
Orally
administered
nanocarriers
play
an
important
role
in
improving
druggability,
promoting
intestinal
absorption,
and
enhancing
therapeutic
applications
for
the
treatment
of
local
systemic
diseases.
However,
delivering
efficiency
cell
response
mucosa
to
orally
is
affected
by
physiological
environment
barriers
gastrointestinal
tract,
physicochemical
properties
nanocarriers,
their
bidirectional
interactions.
Goblet
cells
secrete
form
extracellular
mucus,
which
hinders
movement
nanoparticles.
Meanwhile,
epithelial
may
absorb
NPs,
allowing
transcytosis
or
degradation.
Conversely,
nanoparticle-induced
toxicity
occur
as
a
biological
nanoparticle
exposure.
Additionally,
immune
functions
secretions
such
mucin,
peptide,
cytokines
also
be
altered.
In
this
review,
we
discuss
interactions
between
nanoparticles
focusing
on
enterocytes
goblet
cells,
M
according
essential
crosstalk
with
cells.
Furthermore,
recent
advances
how
physiochemical
influence
interplay,
delivery,
fate
mucosa.
Understanding
different
from
perspective
interaction
provides
support
development,
rational
design,
potency
maximation,
application
advanced
oral
nanocarrier
delivery
systems.
The
formation
of
glutenin
protein
corona
alleviated
gut
microbiota
dysbiosis,
increased
the
short
chain
fatty
acid
production,
improved
barrier
function,
mitigated
mitochondrial
dysfunction,
and
reduced
reactive
oxygen
species.
ACS Nano,
Год журнала:
2024,
Номер
18(52), С. 35310 - 35324
Опубликована: Дек. 16, 2024
The
development
of
effective
oral
drug
delivery
systems
for
targeted
gut-to-liver
transport
remains
a
significant
challenge
due
to
the
multiple
biological
barriers
including
harsh
gastrointestinal
tract
(GIT)
environment
and
complex
protein
corona
(PC)
formation.
In
this
study,
we
developed
ligand-modified
nanoparticles
(NPs)
that
enable
by
crossing
GIT
attenuating
PC
Specifically,
mesoporous
silica
(MSNs)
were
functionalized
with
peptides
targeting
neonatal
Fc
receptor
(FcRn),
capitalizing
on
FcRn
expression
in
small
intestine
liver
delivery.
We
showed
MSNs
decorated
cyclic
binding
peptide
(MSNs-FcBP)
obtained
enhanced
diffusion
intestinal
mucus
superior
transportation
across
compared
unmodified
large
IgG
fragment
(MSNs-Fc),
which
correlated
diminished
adsorption
weaker
interaction
mucin.
After
entering
blood
circulation,
reduced
serum
formation
MSNs-FcBP
reduces
proteolytic
phagocytic
propensity
reticuloendothelial
system,
ultimately
ameliorating
accumulation
hepatocytes.
Pharmacokinetic
pharmacodynamic
studies
diabetic
mice
revealed
effectively
transported
therapeutic
agent
exenatide
epithelium,
leading
hypoglycemic
response
improved
glucose
tolerance.
This
study
underscores
critical
role
ligand
selection
limiting
formation,
thereby
significantly
enhancing
increasing
permeation
minimizing
serum-protein
interactions.
illustrates
potential
strategy
optimize
bioavailability
efficacy.
