title: In vitro and in vivo aspects of N-acyl-phosphatidylethanolamine-containing liposomes.
abstract: Incorporation of the phospholipid, N-acyl-phosphatidylethanolamine (NAPE), has shown to increase the liposomal stability towards plasma components in vitro. Besides increasing the circulation-time, NAPE has been shown to contain fusiogenic properties. Hence, fusion between NAPE-liposomes and target cells may be expected, resulting in a favorable delivery of drug to the target cell. In this study, NAPE has been tested as a potential liposomal component of phosphatidylcholine-liposomes. The liposomes were characterized by size, long-term stability and phase transition temperature (T(m)). In vivo behavior of NAPE-liposomes was determined by the blood-circulation half-life in mice. A characterization of the liposomes revealed that high content of NAPE resulted in liposomes of increased size compared to pure phosphatidylcholine-liposomes. However, the liposomes showed only a slight increase in size during storage for 5 weeks. Determination of T(m) for NAPE-liposomes showed increasing values of T(m) by increasing percentage of NAPE in the liposomal bilayer, due to the higher T(m) of NAPE compared to phosphatidylcholine. Blood-clearance studies showed an initial increase in blood-circulation of liposomes containing high amounts of NAPE. Thus, these results suggest that liposomes containing high percentage of NAPE may be a promising candidate for long-circulating liposomes, possibly in combination with other stabilizing components, e.g. cholesterol.
authors.affiliation: Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark. cv@dfh.dk
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vermehren
authors.forename: Harald S
authors.initials: HS
authors.lastname: Hansen
authors.forename: Brian
authors.initials: B
authors.lastname: Clausen-Beck
authors.forename: Sven
authors.initials: S
authors.lastname: Frøkjaer
mesh_terms: D000731:Androstanes / Q000493:pharmacokinetics; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects / Q000502:physiology; D001776:Blood Circulation Time; D004337:Drug Carriers; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014018:Tissue Distribution; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: C415601:3-oxo-androstan-17-yl-(2'',2'',6'',6''-tetramethyl-N-oxyl)piperidyl butan-1',4'-dioate; D000731:Androstanes; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D014316:Tritium