NEW AMPHIPATIC POLYMER LIPID CONJUGATES FORMING LONG-CIRCULATING RETICULOENDOTHELIAL SYSTEM-EVADING LIPOSOMES

Lipid-conjugates of two amphipatic polymers, poly(2-methyl-2-oxazoline ) (PMOZ) and poly(2-ethyl-2-oxazoline) (PEOZ) (degree of polymerizatio n approximate to 50) were synthesized by linking glutarate esters of t he polymers to distearoylphosphatidylethanolamine (DSPE) or alternativ ely by termination of the polymerization process with DSPE. Surface-mo dified liposomes (90 +/- 5 nm) prepared from either conjugate (5 mol % of total lipid) were injected into rats and followed by blood level a nd tissue distribution measurements. Both polymers PEOZ and PMOZ were found to convey long circulation and low hepatosplenic uptake to lipos omes to the same extent as polyethylene glycol (PEG), the best known m aterial for this purpose. This is the first demonstration of protectio n from rapid recognition and clearance conveyed by alternative polymer s, which is equal to the effect of PEG.