title: Accelerated blood clearance was not induced for a gadolinium-containing PEG-poly(L-lysine)-based polymeric micelle in mice.
abstract: OBJECTIVE
  Accelerated blood clearance (ABC) is induced by repeated injections of PEGylated liposomes. In this study, the ABC was investigated for a gadolinium-containing PEG-poly(L-lysine)-based polymeric micelle (Gd-micelle) and PEGylated liposome (Gd-liposome) in mice.
  
  
  METHODS
  Effects of the first injection of Gd-micelle on the tissue distribution of the second dose of Gd-micelle were studied. Additionally, effects of the first injection of Gd-micelle, Gd-liposome, empty liposome, polyethyleneglycol (PEG(500,000)), and PEG-lipid on the distribution of the second dose of the Gd-liposome were evaluated.
  
  
  RESULTS
  Results indicated that the tissue distribution of the second injection of the Gd-micelle at a dose of 33, 5, or 2 micromol Gd/kg was not affected by the first injection of the Gd-micelle at different doses and time intervals or of the empty PEGylated liposome 7 days before. ABC of Gd-liposome at a dose of 2.3 micromol Gd/kg (corresponding to 10 micromol lipids/kg) was observed when the empty PEGylated liposome or Gd-liposome, but not the Gd-micelle, PEG(500,000) or PEG-lipid, was pre-administered.
  
  
  CONCLUSIONS
  The hydrophobic core of the micelle or lipid bilayer of PEGylated liposome has a major effect on this phenomenon. These studies have significant implications for the evaluation of PEG-poly(L-lysine)-based micellar formulation of Gd-based contrast agents.
authors.affiliation: Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
authors.forename: Huili
authors.initials: H
authors.lastname: Ma
authors.forename: Kouichi
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Takuya
authors.initials: T
authors.lastname: Minowa
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawano
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D005682:Gadolinium / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008823:Micelles; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; C443714:polylysine-graft-(poly(ethylene glycol)); D011107:Polylysine; D011092:Polyethylene Glycols; D005682:Gadolinium