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Sterol-modified PEG lipids: alteration of the bilayer anchoring moiety has an unexpected effect on liposome circulation.

We synthesized and characterized two novel sterol-anchored polyethylene glycols (PEG) as potential alternatives to conventional phosphatidylethanolamine-PEGs. Liposomes containing the dicholesterol anchored PEG at 5 mole percent exhibit canonical PEGgylated-liposome behaviors including retention of encapsulated small molecules, low serum protein adsorption, and reduced cellular uptake yet they do not exhibit long circulation.