Factors Affecting the Accelerated Blood Clearance of Polyethylene Glycol-Liposomes Upon Repeated Injection

Previously, we showed that long-circulating polyethylene glycol (PEG)-liposomes are cleared rapidly from the circulation when injected repeatedly in the same animal. In this article, we de-scribe the effects of PEG-coating, the circulation time, the lipid dose, and the presence of encapsulated doxorubicin on the pharmacokinetics upon repeated injection in rats. Furthermore, the role of liver and splenic macrophages was investigated. Liposomes without PEG-coating also showed the so-called “enhanced clearance effect”: blood levels at 4 h post injection decreased from 62.8 6 13.7 % of injected dose (%ID) after the first injection to 0.54 6 0.21%ID after the second injection. This decrease was independent of the circulation time of the first dose. Decreasing the first lipid dose of PEG-liposomes to 0.05 mmol/kg still led to enhanced clearance of a second dose of