LIPOSOME LEAKAGE AND BLOOD-CIRCULATION - COMPARISON OF ADSORBED BLOCK COPOLYMERS WITH COVALENT ATTACHMENT OF PEG

Adsorption of block copolymers onto colloids is a promising method to reduce their biological interactions leading to phagocytosis that, for liposomes in particular, is challenged by recent competition through covalent coating with polyethyleneglycol (PEG). The interaction of block copolymer emulsifying agents and PEG lipid derivatives with liposomes was investigated for evidence of adsorption though dynamic light scattering measurements of mean particle size distribution and compared with those of entrapped aqueous label efflux. The results show increases in hydrodynamic radius are less than about 3.5 nm, regardless of liposome composition or preparation method. At the same time, efflux of entrapped aqueous label increases indicating that adsorption does occur. Efflux was reduced but not eliminated when the liposomes were prepared with high temperature phase transition lipids. In contrast, efflux was not observed upon addition of the PEG lipid derivative. In vivo studies of liposomes treated with the block copolymer, F-108, showed a moderate increase in blood circulation time, but less than that when the PEG lipid derivative was incorporated.