title: Insertion of poly(ethylene glycol) derivatized phospholipid into pre-formed liposomes results in prolonged in vivo circulation time.
abstract: Transfer of MPEG(1900)-DSPE from micellar phase to pre-formed liposomes imparts long in vivo circulation half-life to an otherwise rapidly cleared lipid composition. MPEG(1900)-DSPE transfers efficiently and quickly in a time and temperature dependent manner. There is negligible content leakage and a strong correlation between assayed mol% MPEG(1900)-DSPE, liposome diameter increase, and pharmacokinetic parameters such as distribution phase half-life. Since a biological attribute (liposome clearance rate) can be modified by the insertion process, it suggests a simple and economical way to impart site-specific targeting to a variety of liposome delivery systems. This method is also a convenient way to measure the 'brush' thickness of such conjugates directly.
authors.affiliation: SEQUUS Pharmaceuticals, Inc., Menlo Park, CA 94025, USA. paulu@sequus.com
authors.forename: P S
authors.initials: PS
authors.lastname: Uster
authors.forename: T M
authors.initials: TM
authors.lastname: Allen
authors.forename: B E
authors.initials: BE
authors.lastname: Daniel
authors.forename: C J
authors.initials: CJ
authors.lastname: Mendez
authors.forename: M S
authors.initials: MS
authors.lastname: Newman
authors.forename: G Z
authors.initials: GZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D008081:Liposomes / Q000493:pharmacokinetics*; D008297:Male; D010714:Phosphatidylethanolamines / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D008081:Liposomes; C099730:N-carbamylmethoxypoly(ethylene glycol)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols