MODULATION OF PHARMACOKINETIC BEHAVIOR OF LIPOSOMES

The authors's recent work on matters pertinent io the in vivo processi ng of systemically administered liposomes is reviewed. Particular emph asis is given to factors influencing blood clearance rates, hepatic an d splenic uptake and intrahepatic as well as intrasplenic distribution . In addition to size, liposomal composition plays a crucial role in d etermining these parameters as was shown by comparing the fate of lipo somes composed of egg phosphatidylcholine (eggPC), cholesterol (Chol) and either phosphatidylglycerol (PG) or different molar fractions of p hosphatidylserine (PS) as negatively charged components. Neutral eggPC /Chol liposomes with and without lipid-anchored poly(ethylene glycol) were also compared. The experimental approach included the measurement of radiolabel distribution from [H-3] cholesterylether-labeled liposo mes in blood, liver and spleen and in isolated hepatic cell fractions as well as morphological observations on colloidal gold containing lip osomes at the light- and electronmicroscopical level. Evidence is pres ented that apolipoprotein-E plays an important role in the clearance a nd hepatic uptake and processing of some liposomes but not of others.