Journal
PHARMACEUTICAL RESEARCH
Volume 27, Issue 2, Pages 296-302Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-009-0018-9
Keywords
accelerated blood clearance; gadolinium; PEGylated liposome; polyethylene glycol (PEG); polymeric micelle
Funding
- Ministry of Health, Labour, and Welfare of Japan
- Program for Promoting the Establishment of Strategic Research Centers
- Special Coordination Funds for Promoting Science and Technology
- Ministry of Education, Culture, Sports, Science and Technology of Japan
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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.
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