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Modulation of pharmacokinetic behavior of liposomes

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Author: Scherphof, G.L. · Velinova, M. · Kamps, J. · Donga, J. · Want, H. van der · Kuipers, F. · Havekes, L. · Daemen, T.
Type:article
Date:1997
Institution: TNO Preventie en Gezondheid
Source:Advanced Drug Delivery Reviews, 2-3, 24, 179-191
Identifier: 233860
doi: doi:/10.1016/S0169-409X(96)00457-7
Keywords: Biology · Blood · Cholesterol · Composition · Controlled drug delivery · Drug interactions · Drug products · Enzyme kinetics · Lipids · Proteins · Apolipoprotein E · Colloidal gold · Endothelial cells · Fenestrations · Hepatocytes · Liposomes · Liver and spleen macrophages · Opsonization · Phosphatidylglycerol · Phosphatidylserine · Pharmacokinetics · Cholesteryl oleyl ether · Colloidal gold · Distearoylphosphatidylethanolamine · Macrogol · Radioisotope · Unclassified drug · Chemical composition · Clearance · Electron microscopy · Internalization · Kupffer cell · Liver · Liver cell · Macrophage · Microscopy · Nonhuman · Opsonization · Particle size · Spleen · Tissue distribution

Abstract

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