PURPOSE: 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. MATERIALS AND 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.
PURPOSE: 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. MATERIALS AND 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: E T Dams; P Laverman; W J Oyen; G Storm; G L Scherphof; J W van Der Meer; F H Corstens; O C Boerman Journal: J Pharmacol Exp Ther Date: 2000-03 Impact factor: 4.030
Authors: P Laverman; M G Carstens; O C Boerman; E T Dams; W J Oyen; N van Rooijen; F H Corstens; G Storm Journal: J Pharmacol Exp Ther Date: 2001-08 Impact factor: 4.030
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Authors: Nazila Kamaly; Zeyu Xiao; Pedro M Valencia; Aleksandar F Radovic-Moreno; Omid C Farokhzad Journal: Chem Soc Rev Date: 2012-03-05 Impact factor: 54.564