THE PRESENCE OF G(M1) IN LIPOSOMES WITH ENTRAPPED DOXORUBICIN DOES NOT PREVENT RES BLOCKADE

The incorporation of ganglioside G(M1) or phosphatidylethanolamine-pol yethyleneglycol conjugates into liposomes can result in extended circu lation lifetimes in vivo. This has been attributed to an ability to av oid uptake by the reticuloendothelial system (RES), specifically the p hagocytic cells of the liver and spleen. Here we examine whether a rep resentative large unilamellar vesicle (LUV) formulation which contains G(M1) (distearoylphosphatidylcholine/cholesterol/G(M1), 45:45: 10 mol /mol), actually does avoid the RES. It is shown that a pre-dose of LUV s which contain G(M1) and entrapped doxorubicin blocks the accumulatio n of subsequently injected empty distearoylphosphatidylcholine/cholest erol liposomes in liver. It is therefore concluded that liposomes exhi biting extended circulation lifetimes can induce RES blockade and do n ot avoid uptake by liver phagocytes.