We describe an efficient method for separating liposomes (large unilamellar
vesicles, 120-150 nm diameter) from plasma lipoproteins employing fast pro
tein liquid chromatography (FPLC), This method resolves very low density li
poprotein (VLDL), low-density lipoprotein, high-density lipoprotein, and ot
her plasma components. Selective detection of liposomes (large unilamellar
vesicles, 120-150 nm diameter) was achieved using either radiolabeled or fl
uorescent lipid probes, The liposomes were found to coelute with the earlie
st FPLC-eluting lipoprotein fraction, VLDL. The remaining plasma lipoprotei
n and protein components eluted at later times and were resolved from lipos
omes and VLDL, In order to separate VLDL from liposomes, we selectively pre
cipitated the VLDL fraction from plasma using tungstophosphoric acid and ma
gnesium chloride, prior to separation by FPLC, Furthermore, we demonstrate
that this technique can be used to separate liposomes from lipoproteins in
plasma samples collected after intravenous administration of liposomes to m
ice. This technique has wide application in studies of liposome stability i
n blood and, in particular, for the characterization of liposomal drug carr
ier systems, (C) 1999 Academic Press.