Effect of repeated intravenous administration on the circulation kinetics of poly(ethyleneglycol)-liposomes in rats

The use of sterically stabilized poly(ethyleneglycol)-coated liposomes (PEG-liposomes) is becoming increasingly important and several preparations based on long-circulating liposomes are already commercially available. From a clinical point of view, it is of importance to study the effect of multiple i.v. administration of PEG-liposomes on their pharmacokinetic behavior. Sterically stabilized liposomes were obtained by incorporation of PEG conjugated to distearoylethanolamine (DSPE) into the liposomal bilayers. Rats received 4 i.v. injections of small (0.12 mu m) PEG-liposomes at 24 or 48 h dosing intervals. Blood levels of liposomal label were determined at several time-points after injection. Our findings demonstrate that, under the chosen conditions, i.v. injection of PEG-liposomes has no effect on the blood circulation kinetics of subsequent doses of similar liposomes given at 24 or 48 h dosing intervals. These findings suggest that PEG-liposomes are suitable as drug carriers for diagnostic and therapeutic applications that require repeated i.v. injections.