Formation and physicochemical properties of polymeric pH-sensitive liposomes

Abstract

With an ultimate aim of targeting cancer drugs entrapped within liposomes to malignant tissues, liposomes containing polymerizable phosphatidyl-ethanolamine and a fatty acid were prepared. For this diacetylenic phosphatidylethanolamine (DAPE), a phosphatidylethanolamine containing diacetylene groups, was synthesized. Liposomes containing DAPE, fatty acid and either phosphatidylethanolamine (PE) or PE-β-oleoyl-γ-palmitoyl (POPE) were prepared. Polymerization of DAPE was effected by UV illumination. The polymeric liposomes were stable at physilogical pH but became unstable below pH 6.5 of various compositions studied, the greatest pH-sensitivity was found with liposomes composed of 35 mol% DAPE/35 mol% POPE/30 mol% and saturated fatty acid. From ethanol addition, aggregation, and permeability tests, polymeric liposomes were found to be more stable than monomeric liposomes. The presence of blood plasma albumin decreased vesicle stability while apolipoprotein A-I had and opposite effect and plasma as a whole had a slightly stabilizing effect.