title: Liposomes with entrapped doxorubicin exhibit extended blood residence times.
abstract: The blood residence time of liposomes with entrapped doxorubicin is shown to be significantly longer than for identically prepared empty liposomes. Liposomal doxorubicin systems with a drug-to-lipid ratio of 0.2 (w/w) were administered at a dose of 100 mg lipid/kg. Both doxorubicin and liposomal lipid were quantified in order to assess in vivo stability and blood residence times. For empty vesicles composed of phosphatidylcholine (PC)/cholesterol (55:45, mole ratio) and sized through filters of 100 nm pore size, 15-25% of the administered lipid dose was recovered in the blood 24 h after i.v. injection. The percentage of the dose retained in the circulation at 24 h increased 2-3-fold when the liposomes contain entrapped doxorubicin. For 100 nm distearoyl PC/chol liposomal doxorubicin systems, as much as 80% of the injected dose of lipid and drug remain within the blood compartment 24 h after i.v. administration.
authors.affiliation: Canadian Liposome Co. Ltd, North Vancouver, Canada.
authors.forename: M B
authors.initials: MB
authors.lastname: Bally
authors.forename: R
authors.initials: R
authors.lastname: Nayar
authors.forename: D
authors.initials: D
authors.lastname: Masin
authors.forename: M J
authors.initials: MJ
authors.lastname: Hope
authors.forename: P R
authors.initials: PR
authors.lastname: Cullis
authors.forename: L D
authors.initials: LD
authors.lastname: Mayer
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D004317:Doxorubicin / Q000097:blood*; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D007700:Kinetics; D008081:Liposomes; D051379:Mice; D008811:Mice, Inbred DBA; D010713:Phosphatidylcholines / Q000097:blood
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D004317:Doxorubicin; D002784:Cholesterol