Expert Opinion on Drug Delivery,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 11, 2025
Introduction
mRNA
therapeutics
were
a
niche
area
in
drug
development
before
COVIDvaccines.
Now
they
are
used
vaccine
development,
for
non-viral
therapeuticgenome
editing,
vivo
chimericantigen
receptor
T
(CAR
T)
celltherapies
and
protein
replacement.
mRNAis
large,
charged,
easily
degraded
by
nucleases.
It
cannot
get
into
cells,escape
the
endosome,
be
translated
to
disease-modifying
without
adelivery
system
such
as
lipid
nanoparticles
(LNPs).
Vaccines,
Journal Year:
2024,
Volume and Issue:
12(2), P. 186 - 186
Published: Feb. 12, 2024
In
recent
years,
lipid
nanoparticles
(LNPs)
have
attracted
extensive
attention
in
tumor
immunotherapy.
Targeting
immune
cells
cancer
therapy
has
become
a
strategy
of
great
research
interest.
mRNA
vaccines
are
potential
choice
for
immunotherapy,
due
to
their
ability
directly
encode
antigen
proteins
and
stimulate
strong
response.
However,
the
mode
delivery
lack
stability
key
issues
limiting
its
application.
LNPs
an
excellent
carrier,
structural
biocompatibility
make
them
effective
means
delivering
specific
targets.
This
study
summarizes
progress
LNP
carrier-assisted
targeted
controlled
release
immunity.
The
role
improving
stability,
immunogenicity,
targeting
is
discussed.
review
aims
systematically
summarize
latest
immunity
provide
new
ideas
strategies
as
well
more
treatment
plans
patients.
Current Opinion in Colloid & Interface Science,
Journal Year:
2023,
Volume and Issue:
66, P. 101705 - 101705
Published: May 22, 2023
Lipid
nanoparticles
(LNPs)
are
the
most
versatile
and
successful
gene
delivery
systems,
notably
highlighted
by
their
use
in
vaccines
against
COVID-19.
LNPs
have
a
well-defined
core–shell
structure,
each
region
with
its
own
distinctive
compositions,
suited
for
wide
range
of
vivo
applications.
Here,
we
discuss
how
detailed
knowledge
LNP
structure
can
guide
formulation
to
improve
efficiency
nucleic
acid
payload.
Perspectives
on
structural
design
more
efficient
transfection.
Views
key
physical
characterization
techniques
needed
such
developments
outlined
including
opinions
biophysical
approaches
both
correlating
functionality
biological
fluids
improving
ability
escape
endosome
deliver
they
Pharmaceutics,
Journal Year:
2024,
Volume and Issue:
16(1), P. 131 - 131
Published: Jan. 19, 2024
Lipid
nanoparticles
(LNPs)
have
gained
prominence
as
primary
carriers
for
delivering
a
diverse
array
of
therapeutic
agents.
Biological
products
achieved
solid
presence
in
clinical
settings,
and
the
anticipation
creating
novel
variants
is
increasing.
These
predominantly
encompass
proteins,
nucleic
acids
messenger
RNA.
The
advancement
efficient
LNP-based
delivery
systems
biologics
that
can
overcome
their
limitations
remains
highly
favorable
formulation
strategy.
Moreover,
given
small
size,
biocompatibility,
biodegradation,
LNPs
proficiently
transport
moiety
into
cells
without
significant
toxicity
adverse
reactions.
This
especially
crucial
existing
upcoming
biopharmaceuticals
since
large
molecules
group
present
several
challenges
be
by
LNPs.
review
describes
LNP
technology
summarizes
developments
chemistry,
manufacturing,
characterization
lipids
used
development
biologics.
Finally,
we
perspective
on
potential
opportunities
current
pertaining
to
technology.
Journal of Biomedical Materials Research Part A,
Journal Year:
2024,
Volume and Issue:
112(9), P. 1494 - 1505
Published: March 15, 2024
RNA-based
therapeutics
have
gained
traction
for
the
prevention
and
treatment
of
a
variety
diseases.
However,
their
fragility
immunogenicity
necessitate
drug
carrier.
Lipid
nanoparticles
(LNPs)
emerged
as
predominant
delivery
vehicle
RNA
therapeutics.
An
important
component
LNPs
is
ionizable
lipid
(IL),
which
protonated
in
acidic
environment
endosome,
prompting
cargo
release
into
cytosol.
Currently,
there
growing
evidence
that
structure
IL
tails
significantly
impacts
efficacy
LNP-mediated
mRNA
translation.
Here,
we
optimized
tail
length
three
different
cargos.
Using
C12-200,
gold
standard
IL,
model,
designed
library
ILs
with
varying
lengths
evaluated
potency
vivo.
We
demonstrated
small
changes
lipophilicity
can
drastically
increase
or
decrease
identified
formulated
firefly
luciferase
(1929
base
pairs)
C10-200,
an
shorter
than
enhance
liver
transfection
by
over
10-fold.
Furthermore,
were
found
to
be
ideal
encapsulating
cargos
sizes.
erythropoietin
(EPO),
responsible
stimulating
red
blood
cell
production,
(858
pairs),
C13-200
led
EPO
translation
at
levels
similar
C12-200
LNP.
The
Cas9
(4521
C9-200
induced
times
quantity
indels
compared
Our
findings
suggest
may
lead
higher
larger
mRNAs,
longer
more
efficacious
delivering
smaller
envision
results
this
project
utilized
future
design
criteria
next
generation
LNP
systems
European Journal of Pharmaceutics and Biopharmaceutics,
Journal Year:
2024,
Volume and Issue:
197, P. 114222 - 114222
Published: Feb. 20, 2024
Lipid
nanoparticles
(LNPs)
employing
ionizable
lipids
are
the
most
advanced
technology
for
delivery
of
RNA,
notably
mRNA,
to
cells.
LNPs
represent
well-defined
core–shell
particles
with
efficient
nucleic
acid
encapsulation,
low
immunogenicity
and
enhanced
efficacy.
While
much
is
known
about
structure
activity
LNPs,
less
attention
given
timing
LNP
uptake,
cytosolic
transfer
protein
expression.
However,
kinetics
a
key
factor
determining
efficiency.
Hence
quantitative
insight
into
multi-cascaded
pathway
interest
elucidate
mechanism
delivery.
Here,
we
review
experiments
as
well
theoretical
modeling
mRNA-release
We
describe
sequence
stochastic
processes
mathematical
model
subsequent
translation
from
mRNA.
compile
probabilities
numbers
obtained
time
resolved
microscopy.
Specifically,
live-cell
imaging
on
single
cell
arrays
(LISCA)
allows
high-throughput
acquisition
thousands
individual
GFP
reporter
expression
courses.
The
traces
yield
distribution
mRNA
life-times,
rates
onset.
Correlation
analysis
reveals
an
inverse
dependence
gene
efficiency
transfection
onset-times.
Finally,
discuss
why
release
critical
in
context
codelivery
multiple
species
case
co-expression
or
CRISPR/Cas
editing.
