title: Influence of lipopolymer concentration on liposome degradation and blood clearance.
abstract: It is well known, that a prolonged liposome circulation time can be achieved by incorporation of lipopolymers into the lipid membrane thereby reducing interactions with destabilizing factors in the blood stream, e.g. phagocytic cells and lipoproteins. However, very little is known about the enzymatic degradation of steric hindered liposomes introduced into body fluids. In this study, the blood clearance and the PLA2 catalyzed degradation of unilamellar dipalmitoylphosphatidylcholine (DPPC) liposomes incorporated with increasing amounts of dipalmitoylphosphatidylethanolamine-polyethyleneglycol (DPPE-PEG), was investigated. The results demonstrated an increase in PLA2 activity for increasing amounts of lipopolymer in the lipid membrane, while the liposome blood clearance was prolonged by incorporation of DPPE-PEG into the liposomes. Hence, these results suggest that it may be possible for long circulating liposomes to obtain a site specific liposome degradation and release of drug substance in tissue with high levels of PLA2.
authors.affiliation: Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Vermehren
authors.forename: K
authors.initials: K
authors.lastname: Jørgensen
authors.forename: S
authors.initials: S
authors.lastname: Frokjaer
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000493:pharmacokinetics*; D000818:Animals; D008081:Liposomes / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D010714:Phosphatidylethanolamines / Q000493:pharmacokinetics*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*
chemical_list: D008081:Liposomes; D010714:Phosphatidylethanolamines; D015060:1,2-Dipalmitoylphosphatidylcholine; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D011092:Polyethylene Glycols; D010741:Phospholipases A; D054467:Phospholipases A2