Modulation of pharmacokinetic behavior of liposomes
article
The authors's recent work on matters pertinent to the in vivo processing of systemically administered liposomes is reviewed. particular emphasis is given to factors influencing blood clearance rates, hepatic and splenic uptake and intrahepatic as well as intrasplenic distribution. In addition to size, liposomal composition plays a crucial role in determining these parameters as was shown by comparing the fate of liposomes composed of egg phosphatidylcholine (eggPC), cholesterol (Chol) and either phosphatidylglycerol (PG) or different molar fractions of phosphatidylserine (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 [3H]cholesterylether-labeled liposomes in blood, liver and spleen and in isolated hepatic cell fractions as well as morphological observations on colloidal gold containing liposomes at the light- and electronmicroscopical level. Evidence is presented that apolipoprotein-E plays an important role in the clearance and hepatic uptake and processing of some liposomes but not of others.
The authors recent work on matters pertinent to the in vivo processing of systemically administered liposomes is reviewed. Particular emphasis is given to factors influencing blood clearance rates, hepatic and splenic uptake and intrahepatic as well as intrasplenic distribution. In addition to size, liposomal composition plays a crucial role in determining these parameters as was shown by comparing the fate of liposomes composed of egg phosphatidylcholine (eggPC), cholesterol (Chol) and either phosphatidylglycerol (PG) or different molar fractions of phosphatidylserine (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 [3H]cholesterylether-labeled liposomes in blood, liver and spleen and in isolated hepatic cell fractions as well as morphological observations on colloidal gold containing liposomes at the light- and electronmicroscopical level. Evidence is presented that apolipoprotein-E plays an important role in the clearance and hepatic uptake and processing of some liposomes but not of others.
Chemicals/CAS: cholesterol, 57-88-5; colloidal gold, 117924-90-0; macrogol, 25322-68-3; phosphatidylcholine, 55128-59-1, 8002-43-5
The authors recent work on matters pertinent to the in vivo processing of systemically administered liposomes is reviewed. Particular emphasis is given to factors influencing blood clearance rates, hepatic and splenic uptake and intrahepatic as well as intrasplenic distribution. In addition to size, liposomal composition plays a crucial role in determining these parameters as was shown by comparing the fate of liposomes composed of egg phosphatidylcholine (eggPC), cholesterol (Chol) and either phosphatidylglycerol (PG) or different molar fractions of phosphatidylserine (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 [3H]cholesterylether-labeled liposomes in blood, liver and spleen and in isolated hepatic cell fractions as well as morphological observations on colloidal gold containing liposomes at the light- and electronmicroscopical level. Evidence is presented that apolipoprotein-E plays an important role in the clearance and hepatic uptake and processing of some liposomes but not of others.
Chemicals/CAS: cholesterol, 57-88-5; colloidal gold, 117924-90-0; macrogol, 25322-68-3; phosphatidylcholine, 55128-59-1, 8002-43-5
Topics
BloodCholesterolCompositionControlled drug deliveryDrug interactionsDrug productsEnzyme kineticsLipidsProteinsApolipoprotein EColloidal goldEndothelial cellsFenestrationsHepatocytesLiposomesLiver and spleen macrophagesOpsonizationPhosphatidylglycerolPhosphatidylserinePharmacokineticsCholesteryl oleyl etherColloidal goldDistearoylphosphatidylethanolamineMacrogolRadioisotopeUnclassified drugChemical compositionClearanceElectron microscopyInternalizationKupffer cellLiverLiver cellMacrophageMicroscopyNonhumanOpsonizationParticle sizeSpleenTissue distribution
TNO Identifier
233860
ISSN
0169409X
Source
Advanced Drug Delivery Reviews, 24(2-3), pp. 179-191.
Pages
179-191
Files
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