N. Oku et al., EFFECT OF SERUM-PROTEIN BINDING ON REAL-TIME TRAFFICKING OF LIPOSOMESWITH DIFFERENT CHARGES ANALYZED BY POSITRON EMISSION TOMOGRAPHY, Biochimica et biophysica acta. Biomembranes, 1280(1), 1996, pp. 149-154
Liposomes have been used as carriers of various materials and as tools
for gene transfer: for the latter purpose, positively charged liposom
es are usually used. To evaluate the stability in the presence of seru
m and the in vivo behavior of such liposomes as well as those aspects
of neutral and negatively charged liposomes, we investigated liposomal
agglutinability in the presence of serum, serum protein binding to th
ese liposomes, and real-time liposomal trafficking by a non-invasive m
ethod using positron emission tomography (PET). Liposomes composed of
dipalmitoylphosphatidylcholine, cholesterol without or with charged li
pid were prepared in the presence of mannitol, and the turbidity chang
e in the presence of serum was determined. Turbidity increase was not
observed for so-called long-circulating liposomes, i.e., liposomes mod
ified with glucuronic acid or with poly(ethylene glycol), or for negat
ively charged liposomes containing dicetyl phosphate (DCP), phosphatid
ylglycerol, or phosphatidylserine. On the contrary, a significant turb
idity increase was observed when positively charged liposomes modified
with stearylamine, stearyltrimethylammmonium chloride or 1,2-dimyrist
yloxypropyl-3-dimethylhydroxyethyl bromide (DMRIE), which is known as
a component of liposomes for gene transfer, were used. These liposomes
were found to have bound a high amount of serum proteins after separa
tion of unbound serum proteins by use of a spin column. The liposomal
trafficking in vivo was determined for three kinds of liposomes, i.e.,
liposomes with DMRIE, those with DCP, and those without charged lipid
s. These liposomes were prepared in the presence of 2-[F-18]fluoro-2-d
eoxy-D-glucose ([2-F-18]FDG), and the [2-F-18]FDG-labeled liposomes we
re administered to mice to perform PET scans. Positively charged lipos
omes containing DMRIE showed high accumulation in the liver compared w
ith neutral and negatively charged liposomes. Since DMRIE-liposomes te
nded to aggregate in the presence of serum, and to be associated with
serum protein, these characters may lead to the high uptake of DMRIE-l
iposomes by the liver.