Formulation of liposomes with a soybean-derived sterylglucoside mixture and cholesterol for liver targeting.
In this study, we investigated a liposomal formulation of dipalmitoylphosphatidylcholine (DPPC) with a soybean-derived sterylglucoside mixture (SG) and cholesterol (Ch) for targeting the liver in mice. We found two distribution profiles of liposomes (reverse-phase evaporation vesicles, REV) in the liver depending on the concentration of Ch and SG in vivo; Ch tends to enhance liposomes containing 10 mol% SG accumulation in the liver, but to decrease those containing 20 mol% SG, and it prolongs the circulation in blood. Dicetylphosphate did not enhance liver targeting by liposomes with SG and Ch. More DPPC/SG/Ch-liposomes (6:1:3) were significantly taken up by cultivated hepatocytes than DPPC/SG/Ch-liposomes (6:0:4), suggesting a glucose residue. The optimal composition for the maximal liver targeting was a mixture of 0.2 micron DPPC/SG/Ch-liposomes (REV) at a molar ratio of 6:1:3. This composition of liposomes was distributed 3 times greater in hepatocytes than non-parenchymal cells 1 h after intravenous injection.
Shimizu
K
K
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Maitani
Y
Y
Takayama
K
K
Nagai
T
T
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000097:blood / Q000737:chemistry*; D002478:Cells, Cultured; D002782:Cholestenes / Q000097:blood / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D003208:Concanavalin A / Q000378:metabolism; D004337:Drug Carriers; D005452:Fluoresceins / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D008081:Liposomes / Q000138:chemical synthesis*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D010316:Particle Size; D037121:Plant Lectins; D013025:Glycine max / Q000737:chemistry*
D002782:Cholestenes; D004337:Drug Carriers; D005452:Fluoresceins; D008081:Liposomes; D037121:Plant Lectins; C096056:soy derived sterylglucoside mixture; D003208:Concanavalin A; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol; C007740:fluorexon