Abstract
Large unilamellar liposomes (LUV), which have a large entrapped volume and efficient drug capture characteristics, are rapidly and efficiently taken up by the RES cells in liver and spleen. A prolonged residence of the drug-entrapped liposomes in the circulation is important for the sustained release of drug form liposomes. Incorporation of 6 mol% of GM1 into LUV composed of DSPC/CH (GM1/DSPC/CH 0.13 : 1 : 1 m/m, 200 nm in size) showed a significant increase of circulation time in the blood circulation. The GM1/DSPC/CH liposomes have been tested for their utility as a sustained release system for adriamycin (ADM) in vivo. ADM was encapsulated into GM1/DSPC/CH liposome with>95% in trapping efficiency by employing the pH gradient method. Mice were given i.p. injection of 2 million L1210 leukemia cells. Twenty-four hrs later, mice were treated with single shot of ADM-GM1/DSPC/CH liposome, ADM-DSPC/CH liposome or free ADM (5 mg/kg). Treatment with ADM-GM1/DSPC/CH liposome significantly increased mean survival times as compared with two controls. Our data indicate that GM1 can significantly enhance the DSPC/CH liposome residence time in bloodstream and GM1/DSPC/CH liposomes with prolonged circulation time are important for the sustained relase of drug in circulation.
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