Accelerated Blood Clearance Was Not Induced for a Gadolinium-Containing PEG-poly(L-lysine)-Based Polymeric Micelle in Mice

作者：Ma Huili; Shiraishi Kouichi; Minowa Takuya; Kawano Kumi; Yokoyama Masayuki; Hattori Yoshiyuki; Maitani Yoshie^*

来源：Pharmaceutical Research, 2010, 27(2): 296-302.

DOI：10.1007/s11095-009-0018-9

• accelerated blood clearance
• gadolinium
• PEGylated liposome
• polyethylene glycol (PEG)
• polymeric micelle

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.
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 indicated that the tissue distribution of the second injection of the Gd-micelle at a dose of 33, 5, or 2 mu mol 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 mu mol Gd/kg (corresponding to 10 mu mol 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.
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.

• 出版日期2010-2
• 单位河北医科大学