Novel pH-sensitive liposomes: liposomes bearing a poly(ethylene glycol) derivative with carboxyl groups.

Three kinds of succinylated poly(glycidol)s were synthesized as poly(ethylene glycol) derivatives having carboxyl groups by the reaction of poly(glycidol) with varying amounts of succinic anhydride in dimethylformamide. These polymers promoted fusion of egg-yolk phosphatidylcholine liposome more intensively with decreasing content of carboxyl groups at pH 7.4, although the extent of fusion was limited. However, the polymer with 56% of succinylated residues induced fusion of the liposome much more strongly at pH 4.0. Egg-yolk phosphatidylcholine liposomes bearing the succinylated poly(glycidol) which was combined with long alkyl chains as anchors to the liposomal membrane were prepared. The leakage of calcein entrapped in the inner aqueous phase of the liposomes was slight at pH 7.4. However, the leakage increased with decreasing pH. The turbidity measurement and the fusion assay indicate that the liposomes bearing the polymer fuse more intensively with decreasing pH and with increasing amount of the polymer bound to the liposomes.