Abstract
Neurotensin-polyplex
nanoparticles
provide
efficient
gene
transfection
of
nigral
dopaminergic
neurons
when
intracerebrally
injected
in
preclinical
trials
Parkinson’s
disease
because
they
do
not
cross
the
blood–brain
barrier
(BBB).
Therefore,
this
study
aimed
to
open
BBB
with
focused
ultrasound
(FUS)
on
substantia
nigra
attain
systemic
and
intranasal
transfections
evaluate
its
detrimental
effect
rats.
Systemically
Evans
Blue
showed
that
a
two-pulse
FUS
opened
BBB.
Accordingly,
35
μL
neurotensin-polyplex
encompassing
green
fluorescent
protein
plasmid
(79.6
nm
mean
size
+
1.3
mV
Zeta-potential)
caused
expression
tyrosine
hydroxylase(+)
cells
(dopaminergic
neurons)
both
substantiae
nigrae
upon
delivery
via
internal
carotid
artery,
retro-orbital
venous
sinus,
or
nasal
mucosa
30
min
after
FUS.
The
intracarotid
yielded
highest
transgene
expression,
followed
by
administration.
However,
neuroinflammation
displayed
infiltrated
lymphocytes
(positive
cluster
differentiation
45),
activated
microglia
ionized
calcium-binding
adaptor
molecule
1),
neurotoxic
A1
astrocytes
glial
fibrillary
acidic
complement
component
3),
neurotrophic
A2
S100
A10),
ended
15
days
Dopaminergic
axonal
projections
decreased
but
recuperated
basal
values
day
transfection,
correlating
decrease
recovery
locomotor
behavior.
In
conclusion,
transient
reversible
neuronal
affection
allowed
nigrae.
could
advance
nanotechnology
clinical
for
disease.
Journal of Cell Science,
Год журнала:
2024,
Номер
137(9)
Опубликована: Май 1, 2024
ABSTRACT
Tight
junctions
(TJs)
are
specialized
regions
of
contact
between
cells
epithelial
and
endothelial
tissues
that
form
selective
semipermeable
paracellular
barriers
establish
maintain
body
compartments
with
different
fluid
compositions.
As
such,
the
formation
TJs
represents
a
critical
step
in
metazoan
evolution,
allowing
multicompartmental
organisms
true,
barrier-forming
epithelia
endothelia.
In
six
decades
have
passed
since
first
observations
by
transmission
electron
microscopy,
much
progress
has
been
made
understanding
structure,
function,
molecular
composition
regulation
TJs.
The
goal
this
Perspective
is
to
highlight
key
concepts
emerged
through
research
future
challenges
lie
ahead
for
field.
International Journal of Pharmaceutics,
Год журнала:
2025,
Номер
670, С. 125186 - 125186
Опубликована: Янв. 8, 2025
The
blood-brain
barrier
(BBB)
plays
a
vital
role
in
protecting
the
central
nervous
system
(CNS)
by
preventing
entry
of
harmful
pathogens
from
bloodstream.
However,
this
also
presents
significant
obstacle
when
it
comes
to
delivering
drugs
for
treatment
neurodegenerative
diseases
and
brain
cancer.
Recent
breakthroughs
nanotechnology
have
paved
way
creation
wide
range
nanoparticles
(NPs)
that
can
serve
as
carriers
diagnosis
therapy.
Regarding
their
promising
properties,
organic
NPs
potential
be
used
effective
drug
delivery
across
BBB
based
on
recent
advancements.
These
remarkable
ability
penetrate
using
various
mechanisms.
This
review
offers
comprehensive
examination
intricate
structure
distinct
properties
BBB,
emphasizing
its
crucial
function
preserving
balance
regulating
transport
ions
molecules.
disruption
conditions
such
stroke,
Alzheimer's
disease,
Parkinson's
disease
highlights
importance
developing
creative
approaches
drugs.
Through
encapsulation
therapeutic
molecules
precise
targeting
processes
vasculature,
NP
formulations
present
hopeful
strategy
improve
BBB.
We
explore
changes
pathological
investigate
factors
affect
successful
into
brain.
In
addition,
we
most
systems
associated
with
shown
positive
results
treating
ischemic
disorders.
opens
up
new
possibilities
nanotechnology-based
therapies
cerebral
diseases.
Abstract
Following
the
discovery
of
bone
as
an
endocrine
organ
with
systemic
influence,
bone-brain
interaction
has
emerged
a
research
hotspot,
unveiling
complex
bidirectional
communication
between
and
brain.
Studies
indicate
that
brain
can
influence
each
other’s
homeostasis
via
multiple
pathways,
yet
there
is
dearth
systematic
reviews
in
this
area.
This
review
comprehensively
examines
interactions
across
three
key
areas:
bone-derived
factors
on
function,
effects
brain-related
diseases
or
injuries
(BRDI)
health,
concept
skeletal
interoception.
Additionally,
discusses
innovative
approaches
biomaterial
design
inspired
by
mechanisms,
aiming
to
facilitate
through
materiobiological
aid
treatment
neurodegenerative
bone-related
diseases.
Notably,
integration
artificial
intelligence
(AI)
highlighted,
showcasing
AI’s
role
expediting
formulation
effective
targeted
strategies.
In
conclusion,
offers
vital
insights
into
mechanisms
suggests
advanced
harness
these
clinical
practice.
These
offer
promising
avenues
for
preventing
treating
impacting
skeleton
brain,
underscoring
potential
interdisciplinary
enhancing
human
health.
Pharmaceutics,
Год журнала:
2024,
Номер
16(7), С. 849 - 849
Опубликована: Июнь 22, 2024
The
state
of
well-being
and
health
our
body
is
regulated
by
the
fine
osmotic
biochemical
balance
established
between
cells
different
tissues,
organs,
systems.
Specific
districts
human
are
defined,
kept
in
correct
functioning,
and,
therefore,
protected
from
exogenous
or
endogenous
insults
both
mechanical,
physical,
biological
nature
presence
barrier
In
addition
to
placental
barrier,
which
even
acts
as
a
linker
two
organisms,
mother
fetus,
all
barriers,
including
blood-brain
(BBB),
blood-retinal
blood-nerve
blood-lymph
blood-cerebrospinal
fluid
operate
maintain
physiological
homeostasis
within
tissues
organs.
From
pharmaceutical
point
view,
most
challenging
undoubtedly
BBB,
since
its
notably
complicates
treatment
brain
disorders.
BBB
action
can
impair
delivery
chemical
drugs
biopharmaceuticals
into
brain,
reducing
their
therapeutic
efficacy
and/or
increasing
unwanted
bioaccumulation
surrounding
healthy
tissues.
Recent
nanotechnological
innovation
provides
advanced
biomaterials
ad
hoc
customized
engineering
functionalization
methods
able
assist
brain-targeted
drug
delivery.
this
context,
lipid
nanocarriers,
synthetic
(liposomes,
solid
nanoparticles,
nanoemulsions,
nanostructured
carriers,
niosomes,
proniosomes,
cubosomes)
cell-derived
ones
(extracellular
vesicles
cell
membrane-derived
nanocarriers),
considered
one
successful
systems
due
reasonable
biocompatibility
ability
cross
BBB.
This
review
aims
provide
complete
up-to-date
view
on
varied
whether
FDA-approved,
involved
clinical
trials,
used
vitro
vivo
studies,
for
inflammatory,
cancerous,
infectious
diseases.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Июль 25, 2024
Depression
is
a
chronic
mental
disorder
characterized
by
persistent
low
mood
and
loss
of
interest.
Treatments
for
depression
are
varied
but
may
not
be
sufficient
cure.
Drug-based
treatment
regimens
have
drawbacks
such
as
slow
onset
action,
bioavailability,
drug
side
effects.
Nanocarrier
Drug
Delivery
Systems
(NDDS)
has
received
increasing
attention
brain
delivery
since
it
assists
the
through
blood-brain
barrier
improves
which
beneficial
treating
depression.
Due
to
particle
size
physicochemical
properties
nanocarriers,
presents
promise
improve
stability
solubility
antidepressants,
thereby
enhancing
concentration.
Moreover,
ligand-modified
nanocarriers
can
taken
target
direct
medicines
release
system
reduce
The
purpose
present
review
provide
an
up-to-date
understanding
relevant
antidepressants
in
different
routes
ingestion,
lay
foundation
patients
with
Microplastics,
particularly
those
in
the
micrometer
scale,
have
been
shown
to
enter
human
body
through
ingestion,
inhalation,
and
dermal
contact.
Recent
research
indicates
that
microplastics
can
potentially
impact
central
nervous
system
(CNS)
by
crossing
blood-brain
barrier
(BBB).
However,
exact
mechanisms
of
their
transport,
uptake,
subsequent
toxicity
at
BBB
remain
unclear.
In
this
study,
we
evaluated
size-dependent
uptake
cytotoxicity
polystyrene
microparticles
using
an
engineered
model.
Our
findings
demonstrate
0.2
μm
exhibit
significantly
higher
transendothelial
transport
compared
1.0
microparticles,
leading
increased
permeability
cellular
damage.
After
24
h
exposure,
15.6-fold
for
particles
2-fold
control.
72
further
27.3-fold
a
4.5-fold
Notably,
administration
following
TNF-α
treatment
resulted
enhanced
absorption
greater
damage
non-stimulated
conditions.
Additionally,
observed
differently
between
2D
cultured
cells
3D
models,
highlighting
importance
testing
models
evaluating
environmental
toxicity.
Pharmaceutics,
Год журнала:
2024,
Номер
16(6), С. 719 - 719
Опубликована: Май 27, 2024
This
review
discusses
the
current
progress
in
clinical
use
of
magnetic
resonance-guided
focused
ultrasound
(MRgFUS)
and
other
platforms
to
transiently
permeabilize
blood-brain
barrier
(BBB)
for
drug
delivery
neurological
disorders
neuro-oncology.
Safety
trials
humans
have
followed
on
from
extensive
pre-clinical
studies,
demonstrating
a
reassuring
safety
profile
paving
way
numerous
translational
Alzheimer’s
disease,
Parkinson’s
primary
metastatic
brain
tumors.
Future
directions
include
improving
devices,
exploring
alternative
approaches
such
as
nanodroplets,
expanding
application
conditions.
Neural Regeneration Research,
Год журнала:
2024,
Номер
20(7), С. 1944 - 1956
Опубликована: Июль 29, 2024
The
blood–brain
barrier
constitutes
a
dynamic
and
interactive
boundary
separating
the
central
nervous
system
peripheral
circulation.
It
tightly
modulates
ion
transport
nutrient
influx,
while
restricting
entry
of
harmful
factors,
selectively
limiting
migration
immune
cells,
thereby
maintaining
brain
homeostasis.
Despite
well-established
association
between
disruption
most
neurodegenerative/neuroinflammatory
diseases,
much
remains
unknown
about
factors
influencing
its
physiology
mechanisms
underlying
breakdown.
Moreover,
role
breakdown
in
translational
failure
therapies
for
disorders
is
just
starting
to
be
understood.
This
review
aims
revisit
this
concept
“blood–brain
breakdown,”
delving
into
controversial
aspects,
prevalent
challenges,
knowledge
gaps
concerning
lack
integrity.
By
moving
beyond
oversimplistic
dichotomy
an
“open”/“bad”
or
“closed”/“good”
barrier,
our
objective
provide
more
comprehensive
insight
dynamics,
identify
novel
targets
and/or
therapeutic
approaches
aimed
at
mitigating
dysfunction.
Furthermore,
review,
we
advocate
considering
diverse
time-
location-dependent
alterations
which
go
tight-junction
endothelial
cell
breakdown,
illustrated
through
dynamics
ischemic
stroke
as
case
study.
Through
exploration,
seek
underscore
complexity
dysfunction
implications
pathogenesis
therapy
diseases.
