Biomaterials Research,
Год журнала:
2023,
Номер
27(1)
Опубликована: Фев. 9, 2023
Conventional
dissolving
microneedles
(DMNs)
face
significant
challenges
in
anti-melanoma
therapy
due
to
the
lack
of
active
thrust
achieve
efficient
transdermal
drug
delivery
and
intra-tumoral
penetration.
In
this
study,
effervescent
cannabidiol
solid
dispersion-doped
(Ef/CBD-SD@DMNs)
composed
combined
components
(CaCO3
&
NaHCO3)
CBD-based
dispersion
(CBD-SD)
were
facilely
fabricated
by
"one-step
micro-molding"
method
for
boosted
tumoral
(CBD).
Upon
pressing
into
skin,
Ef/CBD-SD@DMNs
rapidly
produce
CO2
bubbles
through
proton
elimination,
significantly
enhancing
skin
permeation
penetration
CBD.
Once
reaching
tumors,
can
activate
transient
receptor
potential
vanilloid
1
(TRPV1)
increase
Ca2+
influx
inhibit
downstream
NFATc1-ATF3
signal
induce
cell
apoptosis.
Additionally,
raise
pH
environment
trigger
engineering
tumor
microenvironment
(TME),
including
M1
polarization
tumor-associated
macrophages
(TAMs)
T
cells
infiltration.
The
introduction
not
only
amplify
effect
but
also
provide
sufficient
with
CBD
potentiate
efficacy.
Such
a
"one
stone,
two
birds"
strategy
combines
advantages
effects
on
TME
regulation,
creating
favorable
therapeutic
conditions
obtain
stronger
inhibition
melanoma
growth
vitro
vivo.
This
study
holds
promising
offers
facile
tool
therapies
tumors.
ACS Nano,
Год журнала:
2024,
Номер
18(32), С. 21091 - 21111
Опубликована: Авг. 5, 2024
Milk
exosomes
(mExos)
have
demonstrated
significant
promise
as
vehicles
for
the
oral
administration
of
protein
and
peptide
drugs
owing
to
their
superior
capacity
traverse
epithelial
barriers.
Nevertheless,
certain
challenges
persist
due
intrinsic
characteristics,
including
suboptimal
drug
loading
efficiency,
inadequate
mucus
penetration
capability,
susceptibility
membrane
loss.
Herein,
a
hybrid
vesicle
with
self-adaptive
surface
properties
(mExos@DSPE-Hyd-PMPC)
was
designed
by
fusing
functionalized
liposomes
natural
mExos,
aiming
overcome
limitations
associated
mExos
unlock
full
potential
in
delivery.
The
property
transformation
mExos@DSPE-Hyd-PMPC
achieved
introducing
pH-sensitive
hydrazone
bond
between
highly
hydrophilic
zwitterionic
polymer
phospholipids,
utilizing
pH
microenvironment
on
jejunum
surface.
In
comparison
vesicles
exhibited
2.4-fold
enhancement
encapsulation
efficiency
semaglutide
(SET).
neutrally
charged
surfaces
jejunal
lumen
improved
preservation
proteins
efficient
traversal
barrier.
Upon
reaching
cells,
retained
positively
efficiently
overcame
apical
barrier,
intracellular
transport
basolateral
exocytosis
resulted
an
bioavailability
8.7%
notably
enhanced
pharmacological
therapeutic
effects.
This
study
successfully
addresses
some
holds
overcoming
sequential
absorption
barriers
delivery
peptides.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(2), С. 815 - 815
Опубликована: Янв. 9, 2024
Drugs
based
on
peptides
and
proteins
(PPs)
have
been
widely
used
in
medicine,
beginning
with
insulin
therapy
patients
diabetes
mellitus
over
a
century
ago.
Although
the
oral
route
of
drug
administration
is
preferred
one
by
vast
majority
improves
compliance,
medications
this
kind
due
to
their
specific
chemical
structure
are
typically
delivered
parenterally,
which
ensures
optimal
bioavailability.
In
order
overcome
issues
connected
absorption
PPs
such
as
instability
depending
digestive
enzymes
pH
changes
gastrointestinal
(GI)
system
hand,
but
also
limited
permeability
across
physiological
barriers
(mucus
epithelium)
other
scientists
strenuously
searching
for
novel
delivery
methods
enabling
peptide
protein
drugs
(PPDs)
be
administered
enterally.
These
include
utilization
different
nanoparticles,
transport
channels,
substances
enhancing
permeation,
modifications,
hydrogels,
microneedles,
microemulsion,
proteolytic
enzyme
inhibitors,
cell-penetrating
peptides,
all
extensively
discussed
review.
Furthermore,
article
highlights
PP
therapeutics
both
previously
currently
available
medical
market.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Май 20, 2024
Abstract
The
membrane-fusion-based
internalization
without
lysosomal
entrapment
is
advantageous
for
intracellular
delivery
over
endocytosis.
However,
protein
corona
formed
on
the
membrane-fusogenic
liposome
surface
converts
its
membrane-fusion
performance
to
lysosome-dependent
endocytosis,
causing
poorer
efficiency
in
biological
conditions.
Herein,
we
develop
an
antifouling
effective
vivo.
Leveraging
specific
lipid
composition
at
optimized
ratio,
such
facilitates
fusion
capacity
even
protein-rich
conditions,
attributed
copious
zwitterionic
phosphorylcholine
groups
protein-adsorption
resistance.
Consequently,
demonstrates
robust
membrane-fusion-mediated
medium
with
up
38%
fetal
bovine
serum,
outclassing
two
traditional
liposomes
4%
and
6%
concentrations.
When
injected
into
mice,
can
keep
their
membrane-fusion-transportation
behaviors,
thereby
achieving
efficient
luciferase
transfection
enhancing
gene-editing-mediated
viral
inhibition.
This
study
provides
a
promising
tool
under
complex
physiological
environments,
enlightening
future
nanomedicine
design.
Microneedles
have
emerged
as
a
promising
platform
for
transdermal
drug
delivery
with
prominent
advantages,
such
enhanced
permeability,
mitigated
pain,
and
improved
patient
adherence.
While
microneedles
primarily
been
employed
delivering
small
molecules,
nucleic
acids,
peptides,
proteins,
recent
researches
demonstrated
their
prospect
in
combination
cell
therapy.
Cell
therapy
involving
administration
or
transplantation
of
living
cells
(e.g.
T
cells,
stem
pancreatic
cells)
has
gained
significant
attention
preclinical
clinical
applications
various
disease
treatments.
However,
the
effectiveness
systemic
may
be
restricted
localized
conditions
like
solid
tumors
skin
disorders
due
to
limited
penetration
accumulation
into
lesions.
In
this
perspective,
an
overview
advances
microneedle-assisted
immunotherapy,
tissue
regeneration,
hormone
modulation,
respect
mechanical
property,
loading
capacity,
well
viability
bioactivity
loaded
is
provided.
Potential
challenges
future
perspectives
microneedle-mediated
are
also
discussed.
Abstract
Osteoarthritis
(OA)
is
a
typical
joint
degenerative
disease
that
prevalent
worldwide
and
significantly
affects
the
normal
activities
of
patients.
Traditional
treatments
using
diclofenac
(DCF)
as
an
anti‐inflammatory
drug
by
oral
administration
transdermal
delivery
have
many
inherent
deficiencies.
In
this
study,
lubricating
microneedles
(MNs)
system
for
treatment
osteoarthritis
with
multistage
sustained
great
reduction
in
skin
damage
during
MNs
penetration
developed.
The
bilayer
dissolvable
system,
namely
HA‐DCF@PDMPC,
prepared
designating
composite
material
hyaluronic
acid
(HA)
covalently
conjugated
compound
(HA‐DCF)
tips
then
modifying
surface
self‐adhesive
copolymer
(PDMPC).
designed
to
achieve
release
DCF
via
ester
bond
hydrolysis,
physical
diffusion
from
tips,
breakthrough
lubrication
coating.
Additionally,
reduced
due
presence
coating
on
superficial
surface.
Therefore,
show
good
compliance
patch
OA
treatment,
which
validated
cell
tests
therapeutic
animal
experiments,
down‐regulating
expression
levels
pro‐inflammatory
factors
alleviating
articular
cartilage
destruction.
Acta Pharmaceutica Sinica B,
Год журнала:
2024,
Номер
14(5), С. 2006 - 2025
Опубликована: Фев. 28, 2024
Diabetes,
characterized
by
hyperglycemia,
is
a
major
cause
of
death
and
disability
worldwide.
Peptides,
such
as
insulin
glucagon-like
peptide-1
(GLP-1)
analogs,
have
shown
promise
treatments
for
diabetes
due
to
their
ability
mimic
or
enhance
insulin's
actions
in
the
body.
Compared
subcutaneous
injection,
oral
administration
anti-diabetic
peptides
preferred
approach.
However,
biological
barriers
significantly
reduce
efficacy
peptide
therapeutics.
Recent
advancements
drug
delivery
systems
formulation
techniques
greatly
improved
therapeutics
treating
diabetes.
This
review
will
highlight
(1)
benefits
therapeutics;
(2)
delivery,
including
pH
enzyme
degradation,
intestinal
mucosa
barrier,
biodistribution
barrier;
(3)
platforms
overcome
these
barriers.
Additionally,
discuss
prospects
this
field.
The
information
provided
serve
valuable
guide
future
developments
Journal of Controlled Release,
Год журнала:
2025,
Номер
380, С. 875 - 891
Опубликована: Фев. 19, 2025
Peptides
represent
a
rapidly
expanding
class
of
drugs
with
broad
therapeutic
potential.
However,
due
to
their
large
molecular
weight
and
susceptibility
degradation
in
the
gastrointestinal
tract,
most
peptide
are
administered
via
subcutaneous
(SC)
injections.
Despite
extensive
research,
painless
delivery
platform
for
these
is
still
lacking.
Recently,
an
octopus-inspired
buccal
patch
has
shown
promise
addressing
this
challenge
by
leveraging
synergistic
combination
mechanical
stretching
permeation
enhancers.
In
study,
loaded
formulation
were
optimized
improve
ease
use,
scalability,
efficacy.
Through
assessments
properties,
finite
element
simulations,
ex
vivo
experiments,
we
evaluated
effects
design
material,
as
well
drug
matrix
composition
preparation
methods
on
performance.
A
>
9-fold
larger
effective
surface
area,
produced
mold
casting
medical-grade
silicone
(shore
hardness
50)
lyophilized
matrix,
emerged
promising
system.
beagle
dogs,
30-min
application
resulted
14.6
%
bioavailability
teriparatide
(4118
g
mol-1),
while
semaglutide
(4114
mol-1)
was
9.6
times
higher
than
commercial
tablet.
This
works
showcases
how
systematic
optimization
technology
can
simplify
administration
macromolecular
drugs,
facilitating
clinical
translation
non-invasive
dosage
form.
