ACS Pharmacology & Translational Science,
Год журнала:
2022,
Номер
5(5), С. 278 - 298
Опубликована: Май 2, 2022
Achieving
synergism,
often
by
combination
therapy
via
codelivery
of
chemotherapeutic
agents,
remains
the
mainstay
treating
multidrug-resistance
cases
in
cancer
and
microbial
strains.
With
a
typical
core–shell
architecture
surface
functionalization
to
ensure
facilitated
targeting
tissues,
nanocarriers
are
emerging
as
promising
platform
toward
gaining
such
synergism.
Co-encapsulation
disparate
theranostic
agents
nanocarriers─from
molecules
imaging
or
photothermal
modalities─can
not
only
address
issue
protecting
labile
drug
payload
from
hostile
biochemical
environment
but
may
also
optimized
release
synergistic
effect.
However,
fate
co-encapsulated
molecules,
influenced
temporospatial
proximity,
unpredictable
marred
with
events
deleterious
impact
on
therapeutic
efficacy,
including
molecular
rearrangement,
aggregation,
denaturation.
Thus,
more
than
just
an
art
confining
multiple
therapeutics
into
3D
nanoscale
space,
nanocarrier,
while
aiming
for
should
strive
achieving
harmonious
cohabitation
encapsulated
that,
despite
proximity
opportunities
interaction,
remain
innocuous
each
other
integrity.
This
account
will
inspect
current
progress
co-encapsulation
distill
out
key
points
accomplishing
synergism
through
reciprocity.
Diagnostics,
Год журнала:
2023,
Номер
13(11), С. 1835 - 1835
Опубликована: Май 24, 2023
Immunoassays,
which
have
gained
popularity
in
clinical
practice
and
modern
biomedical
research,
play
an
increasingly
important
role
quantifying
various
analytes
biological
samples.
Despite
their
high
sensitivity
specificity,
as
well
ability
to
analyze
multiple
samples
a
single
run,
immunoassays
are
plagued
by
the
problem
of
lot-to-lot
variance
(LTLV).
LTLV
negatively
affects
assay
accuracy,
precision,
leading
considerable
uncertainty
reported
results.
Therefore,
maintaining
consistency
technical
performance
over
time
presents
challenge
reproducing
immunoassays.
In
this
article,
we
share
our
two-decade-long
experience
delve
into
reasons
for
locations
LTLV,
explore
methods
mitigate
its
effects.
Our
investigation
identifies
potential
contributing
factors,
including
quality
fluctuation
critical
raw
materials
deviations
manufacturing
processes.
These
findings
offer
valuable
insights
developers
researchers
working
with
immunoassays,
emphasizing
importance
considering
development
application.
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(21), С. 13428 - 13428
Опубликована: Ноя. 3, 2022
Inhibition
of
fibril
formation
is
considered
a
possible
treatment
strategy
for
amyloid-related
diseases.
Understanding
the
molecular
nature
inhibitor
action
crucial
design
drug
candidates.
In
present
review,
we
describe
common
kinetic
models
and
classify
known
inhibitors
by
mechanism
their
interactions
with
aggregating
protein
its
oligomers.
This
determines
step
or
steps
aggregation
process
that
become
inhibited
observed
changes
in
kinetics
equilibrium
formation.
The
results
numerous
studies
indicate
approaches
to
antiamyloid
discovery
include
search
strong
binders
monomers,
cappers
blocking
ends
growing
fibril,
species
absorbing
on
surface
oligomers
preventing
nucleation.
Strongly
binding
stabilizing
native
state
can
be
promising
structured
proteins
while
designing
candidates
targeting
disordered
challenging.
ACS Applied Nano Materials,
Год журнала:
2023,
Номер
6(10), С. 8705 - 8716
Опубликована: Май 16, 2023
To
explore
the
impact
of
polymer-coated
silver
nanoparticles
(PC-AgNPs)
on
extent
insulin
aggregation
process,
herein,
we
have
synthesized
three
copolymers
comprising
poly(ethylene
glycol)
methyl
ether
methacrylate
(PEGMA)
and
tert-butoxycarbonyl
(Boc)-protected
amino
acid
(alanine,
leucine,
phenylalanine)
containing
monomers,
via
reversible
addition-fragmentation
chain
transfer
(RAFT)
polymerization.
After
deprotection
Boc
groups,
as-prepared
water-soluble
were
coated
(Ag
NPs),
role
these
NPs
pathways
was
examined
by
multifarious
spectroscopic
microscopic
techniques.
The
inhibitory
effect
against
fibrillation
process
found
to
be
related
surface
properties
NPs,
with
highest
detected
for
phenylalanine-based
Ag
(PPhe-AgNPs).
Using
circular
dichroism
(CD)
spectroscopy
Nile
red
(NR)
fluorescence
spectroscopy,
investigated
conformational
changes
hydrophobic
interaction
in
inhibiting
upon
treatment
PC-AgNPs.
Furthermore,
PC-AgNPs
also
able
disintegrate
matured
fibrils
efficiently
decreased
fibril-induced
cytotoxicity,
as
confirmed
transmission
electron
microscopy
(TEM)
hemolysis
study,
respectively.
Together,
our
findings
established
novel
acid-based
potent
nanomaterials
77–96%
fibril
inhibition
marked
disaggregation
fibrils.
Advanced Healthcare Materials,
Год журнала:
2023,
Номер
12(17)
Опубликована: Фев. 23, 2023
Abstract
Protein
storage
and
delivery
are
crucial
for
biomedical
applications
such
as
protein
therapeutics
recombinant
proteins.
Lack
of
proper
protocols
results
in
the
denaturation
proteins,
rendering
them
inactive
manifesting
undesired
side
effects.
In
this
study,
polyampholyte‐based
(succinylated
ε
‐poly‐
l
‐lysine)
hydrogels
containing
polyvinyl
alcohol
polyethylene
glycol
polymer
matrices
to
stabilize
proteins
developed.
These
facilitated
loading
release
therapeutic
amounts
withstood
thermal
freezing
stress
(15
freeze–thaw
cycles
temperatures
−80
°C
37
°C),
without
resulting
aggregation.
To
best
our
knowledge,
strategy
has
not
been
applied
design
constituting
polymers,
(in
particular,
polymers)
which
have
inherent
efficiency
protect
from
denaturation.
Our
findings
can
open
up
new
avenues
biopharmaceutics
materials
that
store
long‐term
under
severe
safely
deliver
them.
International Journal of Pharmaceutics,
Год журнала:
2023,
Номер
650, С. 123679 - 123679
Опубликована: Дек. 6, 2023
Protein
degradation
is
a
major
concern
for
protein-based
therapeutics.
It
may
alter
the
biological
activity
of
product
and
raise
potential
undesirable
effects
on
patients.
Among
numerous
drivers
protein
degradation,
shear
stress
has
been
focus
around
which
much
work
revolved
since
1970s.
In
pharmaceutical
realm,
often
processed
through
several
unit
operations,
include
mixing,
pumping,
filtration,
filling,
atomization.
Nonetheless,
drug
might
be
exposed
to
significant
stresses,
cooperatively
contribute
together
with
interfacial
stress.
This
review
presents
fundamentals
about
structure,
followed
by
an
overview
degradation.
The
impact
stability
in
different
operations
then
presented,
recommendations
limiting
adverse
biopharmaceutical
formulations
are
outlined.
Finally,
devices
used
explore
discussed.
Molecular Pharmaceutics,
Год журнала:
2024,
Номер
21(3), С. 1137 - 1148
Опубликована: Янв. 26, 2024
Though
protein
stability
and
aggregation
have
been
well
characterized
in
dilute
solutions,
the
influence
of
a
confining
environment
that
exists
(e.g.,
intercellular
tissue
spaces
therapeutic
formulations)
on
structure
is
largely
unknown.
Herein,
effects
confinement
were
explored
for
proteins
different
sizes,
stability,
hydrophobicity
when
encapsulated
hydrophilic
poly(ethylene
glycol)
hydrogels.
Denaturation
curves
show
linear
correlations
between
size
(mesh
size)
thermodynamic
i.e.,
unfolding
free
energy
surface
area
accessible
solvation
(represented
by
m-value).
Two
clusters
types
are
identifiable
from
these
correlations;
defined
differences
area,
propensity.
Proteins
with
higher
larger
lower
propensity
lysozyme
myoglobin)
less
affected
imposed
mesh
than
smaller
growth
hormone
aldehyde
dehydrogenase).
According
to
kinetics
measured
thioflavin
T
fluorescence,
sizes
resulted
slower
rates
sizes.
Compared
buffer
solution,
hydrophobic
human
insulin)
hydrogels
accelerates
aggregation.
Conversely,
amylin)
decelerates
or
prevents
aggregation,
inversely
proportional
size.
These
findings
provide
new
insights
into
conformational
confined
microenvironments
relevant
various
cellular,
tissue,
therapeutics
scenarios.
