Glucose-sensitive liposomes incorporating hydrophobically modified glucose oxidase.

Glucose-sensitive liposomes were prepared by incorporating hydrophobically modified glucose oxidase (EC 1.1.3.4.) into the liposomal bilayer of dioleoylphosphatidylethanolamine and cholesteryl hemisuccinate. For the release test, calcein, a fluorescence marker, was entrapped in the liposomes. The liposomes were stable under neutral conditions in terms of calcein release but an extensive release was observed under acidic conditions. In the experiment of glucose concentration-dependent calcein release, no release was observed for 180 min when the suspension of liposome was free of glucose. With a glucose concentration of 50 mg/dL, no appreciable amount of calcein was released for the first 20 min, and then the release rate was accelerated. At 200 mg/dL glucose concentration which is diagnostic and indicative for insulin-dependent diabetes, the lag time of calcein release became shorter and a faster response was obtained. When glucose concentration further increased to 400 mg/dL, the calcein release rate and the degree of release in 180 min were almost the same as the values when the glucose concentration was 200 mg/dL. The glucose concentration-dependent release is due to pH change, since the suspension of liposomes became acidic during the release experiments.