ACS Nano,
Journal Year:
2022,
Volume and Issue:
16(9), P. 14792 - 14806
Published: Aug. 29, 2022
Despite
lipid
nanoparticles'
(LNPs)
success
in
the
effective
and
safe
delivery
of
mRNA
vaccines,
an
inhalation-based
therapy
for
lung
diseases
remains
challenging.
LNPs
tend
to
disintegrate
due
shear
stress
during
aerosolization,
leading
ineffective
delivery.
Therefore,
need
remain
stable
through
process
nebulization
mucus
penetration,
yet
labile
enough
endosomal
escape.
To
meet
these
opposing
needs,
we
utilized
PEG
enhance
surficial
stability
with
inclusion
a
cholesterol
analog,
β-sitosterol,
improve
Increased
concentrations
enhanced
resistance
while
β-sitosterol
provided
polyhedral
shape,
facilitating
The
optimized
exhibited
uniform
particle
distribution,
morphology,
rapid
mucosal
diffusion
gene
transfection.
Inhaled
led
localized
protein
production
mouse
without
pulmonary
or
systemic
toxicity.
Repeated
administration
sustained
lungs.
Lastly,
encoding
cystic
fibrosis
transmembrane
conductance
regulator
(CFTR)
was
delivered
after
CFTR-deficient
animal
model,
resulting
expression
this
therapeutic
protein.
This
study
demonstrated
rational
design
approach
clinical
translation
inhalable
LNP-based
therapies.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(3), P. 2700 - 2700
Published: Jan. 31, 2023
mRNA
vaccines
have
been
demonstrated
as
a
powerful
alternative
to
traditional
conventional
because
of
their
high
potency,
safety
and
efficacy,
capacity
for
rapid
clinical
development,
potential
rapid,
low-cost
manufacturing.
These
progressed
from
being
mere
curiosity
emerging
COVID-19
pandemic
vaccine
front-runners.
The
advancements
in
the
field
nanotechnology
developing
delivery
vehicles
are
highly
significant.
In
this
review
we
summarized
each
every
aspect
vaccine.
article
describes
structure,
its
pharmacological
function
immunity
induction,
lipid
nanoparticles
(LNPs),
upstream,
downstream,
formulation
process
Additionally,
trials
also
described.
A
deep
dive
into
future
perspectives
vaccines,
such
freeze-drying,
systems,
LNPs
targeting
antigen-presenting
cells
dendritic
cells,
summarized.
Advanced Materials,
Journal Year:
2023,
Volume and Issue:
35(51)
Published: May 17, 2023
Abstract
Messenger
RNA
(mRNA)
has
received
great
attention
in
the
prevention
and
treatment
of
various
diseases
due
to
success
coronavirus
disease
2019
(COVID‐19)
mRNA
vaccines
(Comirnaty
Spikevax).
To
meet
therapeutic
purpose,
it
is
required
that
must
enter
target
cells
express
sufficient
proteins.
Therefore,
development
effective
delivery
systems
necessary
crucial.
Lipid
nanoparticle
(LNP)
represents
a
remarkable
vehicle
indeed
accelerated
applications
humans,
as
several
mRNA‐based
therapies
have
already
been
approved
or
are
clinical
trials.
In
this
review,
focus
on
mRNA‐LNP‐mediated
anticancer
therapy.
It
summarizes
main
strategies
mRNA‐LNP
formulations,
discusses
representative
approaches
cancer,
points
out
current
challenges
possible
future
directions
research
field.
hoped
these
delivered
messages
can
help
further
improve
application
technology
cancer
Journal of Controlled Release,
Journal Year:
2022,
Volume and Issue:
345, P. 819 - 831
Published: March 25, 2022
The
broad
clinical
application
of
mRNA
therapeutics
has
been
hampered
by
a
lack
delivery
vehicles
that
induce
protein
expression
in
extrahepatic
organs
and
tissues.
Recently,
it
was
shown
to
the
spleen
or
lungs
is
possible
upon
addition
charged
lipid
standard
four-component
nanoparticle
formulation.
This
approach,
while
effective,
further
complicates
an
already
complex
drug
formulation
potential
slow
regulatory
approval
adversely
impact
manufacturing
processes.
We
were
thus
motivated
maintain
system
achieving
shifts
tropism.
To
end,
we
replaced
helper
lipidoid
nanoparticles,
DOPE,
with
one
eight
alternatives.
These
lipids
included
neutral
lipids,
DOPC,
sphingomyelin,
ceramide;
anionic
phosphatidylserine
(PS),
phosphatidylglycerol,
phosphatidic
acid;
cationic
DOTAP
ethyl
phosphatidylcholine.
While
maintained
liver,
shifted
lungs,
respectively.
For
example,
replacing
DOPE
increased
positive
LNP
surface
charge
at
pH
7
5-fold
altered
ratio
liver
lung
from
36:1
1:56.
Similarly,
PS
reduced
half
8:1
1:3.
Effects
consistent
across
ionizable
chemistries.
Regarding
mechanism,
nanoparticles
formulated
best
transfected
epithelial
immune
cells,
Further,
lung-tropic
effect
linked
cell
infiltration
compared
lipids.
Together,
these
data
show
intravenous
non-hepatocellular
readily
achievable
maintaining
modified
chemistry.
ACS Nano,
Journal Year:
2022,
Volume and Issue:
16(9), P. 14792 - 14806
Published: Aug. 29, 2022
Despite
lipid
nanoparticles'
(LNPs)
success
in
the
effective
and
safe
delivery
of
mRNA
vaccines,
an
inhalation-based
therapy
for
lung
diseases
remains
challenging.
LNPs
tend
to
disintegrate
due
shear
stress
during
aerosolization,
leading
ineffective
delivery.
Therefore,
need
remain
stable
through
process
nebulization
mucus
penetration,
yet
labile
enough
endosomal
escape.
To
meet
these
opposing
needs,
we
utilized
PEG
enhance
surficial
stability
with
inclusion
a
cholesterol
analog,
β-sitosterol,
improve
Increased
concentrations
enhanced
resistance
while
β-sitosterol
provided
polyhedral
shape,
facilitating
The
optimized
exhibited
uniform
particle
distribution,
morphology,
rapid
mucosal
diffusion
gene
transfection.
Inhaled
led
localized
protein
production
mouse
without
pulmonary
or
systemic
toxicity.
Repeated
administration
sustained
lungs.
Lastly,
encoding
cystic
fibrosis
transmembrane
conductance
regulator
(CFTR)
was
delivered
after
CFTR-deficient
animal
model,
resulting
expression
this
therapeutic
protein.
This
study
demonstrated
rational
design
approach
clinical
translation
inhalable
LNP-based
therapies.
