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Suppression in mice of immunosurveillance against PEGylated liposomes by encapsulated doxorubicin.
[severe combined immunodeficiency]
PEGylated
liposomes
(
PEG-
lip
)
can
escape
from
recognition
by
immune
system
and
show
a
longer
half
-life
in
the
blood
than
non-
PEGylated
liposomes
.
In
this
study
,
we
investigated
the
influence
of
injected
PEG-
lip
encapsulating
doxorubicin
(
PEG-
lip
-DOX
)
on
the
biodistribution
of
subsequently
injected
PEG-
lip
in
mice
.
PEG-
lip
-DOX
,
free
doxorubicin
or
empty
PEG-
lip
were
initially
injected
into
BALB
/
c
mice
via
a
tail
vein
,
and
3
days
later
[
(
3
)
H
]
-
labeled
PEG-
lip
(
[
(
3
)
H
]
PEG-
lip
)
were
injected
into
these
same
mice
.
At
24
h
after
the
injection
,
the
distribution
of
[
(
3
)
H
]
PEG-
lip
in
the
liver
and
spleen
was
significantly
reduced
in
the
PEG-
lip
-DOX
group
compared
with
that
in
the
free
doxorubicin
or
PEG-
lip
group
.
Consequently
,
the
plasma
concentration
of
[
(
3
)
H
]
PEG-
lip
was
significantly
elevated
by
the
pretreatment
with
PEG-
lip
-DOX
.
Altered
pharmacokinetics
was
observed
at
least
until
72
h
after
the
injection
of
[
(
3
)
H
]
PEG-
lip
.
The
influence
of
the
injected
PEG-
lip
-DOX
on
the
pharmacokinetics
of
the
subsequently
injected
[
(
3
)
H
]
PEG-
lip
was
clearly
observed
from
1
to
14
days
,
and
slightly
observed
on
days
21
and
28
,
after
the
injection
of
the
PEG-
lip
-DOX
.
Flow
cytometric
analysis
showed
that
the
number
of
liver
Kupffer
cells
was
significantly
reduced
after
the
treatment
with
PEG-
lip
-DOX
.
On
the
other
hand
,
a
similar
alteration
in
the
distribution
of
the
subsequently
injected
[
(
3
)
H
]
PEG-
lip
was
observed
in
immunodeficient
mice
such
as
BALB
/
c
nu
/
nu
and
severe
combined
immunodeficiency
(
SCID
)
mice
.
These
findings
suggest
that
immune
cells
including
liver
Kupffer
cells
responsible
for
recognizing
PEG-
lip
were
selectively
damaged
by
the
encapsulated
doxorubicin
in
PEG-
lip
injected
initially
,
which
damage
led
to
prolongation
of
the
half
-life
of
subsequently
injected
[
(
3
)
H
]
PEG-
lip
in
the
blood
.