pH-sensitive liposomes composed of tocopherol hemisuccinate and of phosphatidylethanolamine including tocopherol...

The ionic single-chain amphiphile tocopherol hemisuccinate (THS) is water-insoluble but on addition of NaOH, forms vesicles which give an aqueous suspension that is pale-colored and milky. Observation of the permeability of the 5(6)-carboxy-fluorescein-entrapped THS vesicle membranes indicated them to be pH-sensitive liposomes which are stable in the neutral pH region but become leaky at acidic pH. 1-Palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) itself is difficult to form stable liposomes near neutral pH in isotonic buffer but when mixed with THS, gives stable liposomes near physiological pH. These liposomes were found to have a pH-sensitivity that depended on the lipid composition. They were unstable in the presence of rat serum but significantly increased their stability when cholesterol was incorporated (THS/POPE/Chol = 2:8:8). This paper discusses why the ionic single-chain amphiphile THS can form liposome-like vesicles by itself like phosphatidylcholine, which has the diacyl chain.