ABSTRACT
As described previously1-4 and elsewhere in this book, liposomes containing phospholipids with poly(ethylene glycol) covalently attached to their polar headgroups (PEG-lipids) are currently being developed for in vivo delivery of drugs to tumors and other sites in the body. A key feature of these PEG-liposomes is that, when injected into the bloodstream, they have a greatly increased circulation time compared to conventional liposomes.1·5-10 Whereas conventionalliposomes are quickly removed from the blood circulation by macrophages primarily located in the spleen and liver, PEG-liposomes tend to remain in the bloodstream for extended periods of time. This means that PEG-liposomes can be used to deliver drugs by being targeted to specific sites in the bodyP For example, since the microvasculature in some solid tumors is relatively leaky, PEG-liposomes extravasate and accumulate in those tumors.4·9·11-16 The mechanism by which PEG-liposomes avoid macrophages and stay in the blood circulation is thought to involve a "steric barrier" formed around the liposome by the attached PEG molecules.7•9·16-19 It has been argued that such a barrier could sterically prevent contact between liposomes and opsonins, proteolipids, or macrophage cell surfaces. 10·17 The effectiveness of this barrier appears to depend on the incorporation of a sufficient concentration of PEG-lipids, with appropriately sized PEGs, into liposomes.
