Computational Methods for Modeling Lipid-Mediated Active Pharmaceutical Ingredient Delivery
Molecular Pharmaceutics,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 29, 2025
Lipid-mediated
delivery
of
active
pharmaceutical
ingredients
(API)
opened
new
possibilities
in
advanced
therapies.
By
encapsulating
an
API
into
a
lipid
nanocarrier
(LNC),
one
can
safely
deliver
APIs
not
soluble
water,
those
with
otherwise
strong
adverse
effects,
or
very
fragile
ones
such
as
nucleic
acids.
However,
for
the
rational
design
LNCs,
detailed
understanding
composition-structure-function
relationships
is
missing.
This
review
presents
currently
available
computational
methods
LNC
investigation,
screening,
and
design.
The
state-of-the-art
physics-based
approaches
are
described,
focus
on
molecular
dynamics
simulations
all-atom
coarse-grained
resolution.
Their
strengths
weaknesses
discussed,
highlighting
aspects
necessary
obtaining
reliable
results
simulations.
Furthermore,
machine
learning,
i.e.,
data-based
approach
to
lipid-mediated
introduced.
data
produced
by
experimental
theoretical
provide
valuable
insights.
Processing
these
help
optimize
LNCs
better
performance.
In
final
section
this
Review,
computer
reviewed,
specifically
addressing
compatibility
Language: Английский
Revisiting lipid nanoparticle composition and structure: A critical take on simulation approaches
Proceedings of the National Academy of Sciences,
Journal Year:
2025,
Volume and Issue:
122(9)
Published: Feb. 24, 2025
Emotions
coordinate
our
behavior
and
physiological
states
during
survival-salient
events
pleasurable
interactions.
Even
though
we
are
often
consciously
aware
of
current
emotional
state,
such
as
anger
or
happiness,
the
mechanisms
giving
...Emotions
felt
in
body,
somatosensory
feedback
has
been
proposed
to
trigger
conscious
experiences.
Here
reveal
maps
bodily
sensations
associated
with
different
emotions
using
a
unique
topographical
self-report
method.
In
...
Language: Английский
Capturing the Dynamic Integrity of Carbocyanine Fluorophores-based Lipid Nanoparticles by the FRET technique
Journal of Materials Chemistry B,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
Nanoparticles
capable
of
dynamically
reporting
their
structural
integrity
in
real-time
are
a
powerful
tool
to
guide
the
design
drug
delivery
technologies.
Language: Английский
Reply to Trollmann et al.: Perspective on LNP structure and simulation
Proceedings of the National Academy of Sciences,
Journal Year:
2025,
Volume and Issue:
122(9)
Published: Feb. 24, 2025
Emotions
coordinate
our
behavior
and
physiological
states
during
survival-salient
events
pleasurable
interactions.
Even
though
we
are
often
consciously
aware
of
current
emotional
state,
such
as
anger
or
happiness,
the
mechanisms
giving
...Emotions
felt
in
body,
somatosensory
feedback
has
been
proposed
to
trigger
conscious
experiences.
Here
reveal
maps
bodily
sensations
associated
with
different
emotions
using
a
unique
topographical
self-report
method.
In
...
Language: Английский
Recent strategies for enhanced delivery of mRNA to the lungs
Nanomedicine,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 27
Published: April 7, 2025
mRNA-based
therapies
have
emerged
as
a
transformative
tool
in
modern
medicine,
gaining
significant
attention
following
their
successful
use
COVID-19
vaccines.
Delivery
to
the
lungs
offers
several
compelling
advantages
for
mRNA
delivery.
The
are
one
of
most
vascularized
organs
body,
which
provides
an
extensive
surface
area
that
can
facilitate
efficient
drug
transport.
Local
delivery
bypasses
gastrointestinal
degradation,
potentially
enhancing
therapeutic
efficacy.
In
addition,
capillary
network
ideal
target
systemic
However,
developing
effective
presents
challenges.
complex
anatomy
and
body's
immune
response
foreign
particles
create
barriers
This
review
discusses
key
approaches
overcoming
these
challenges
improving
lungs.
It
examines
both
local
strategies
aimed
at
lung
while
mitigating
off-target
effects.
Although
substantial
progress
has
been
made
lung-targeted
therapies,
remain
optimizing
cellular
uptake
achieving
efficacy
within
pulmonary
tissues.
continued
refinement
enhance
lung-specific
targeting
minimizing
degradation
is
critical
clinical
success
therapies.
Language: Английский
Mechanistic Insight into pH-Driven Phase Transition of Lipid Nanoparticles
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 29, 2024
Lipid
nanoparticles
(LNPs)
are
essential
delivery
vehicles
in
mRNA-based
vaccines,
with
their
functionality
largely
governed
by
aminolipids.
At
low
pH,
protonated
aminolipids
facilitate
efficient
mRNA
encapsulation,
while
deprotonation
at
physiological
pH
drives
LNP
remodeling
into
a
stable
spherical
structure,
potentially
aiding
release
during
endosomal
re-protonation
and
concomitant
restructuring
pH.
Our
study
uncovers
the
pH-dependent
phase
transition
of
Comirnaty
lipid
formulation
molecular
scale,
highlighting
intricate
interplay
between
reorganization
aminolipid
protonation.
We
observe
substantial
shift
pKa,
from
7-8
surface
to
below
4
within
hydrophobic
core,
resulting
an
overall
apparent
pKa
nanoparticle
6.3.
The
protonation
significantly
affects
aminolipid's
localization,
enriched
vicinity
neutral
monolayer
covering
LNPs
comprises
cholesterol
(60-65%),
helper
phospholipids
(20-25%),
PEGylated
lipids
(5%),
mix
deprotonated
(5-10%).
These
findings
provide
mechanistic
insights
behavior
LNPs,
offering
foundation
for
optimizing
design
enhance
stability,
tunable
responses,
therapeutic
efficacy.
Language: Английский