Liposomes with phosphatidylethanol as a carrier for oral delivery of insulin: studies in the rat

In this study, phosphatidylethanol formed by phospholipase D catalysed transphosphatidylation of phosphatidylcholine was employed as a component for preparation of liposomal carrier for oral delivery of insulin. Thermotropic behaviour of liposomes from mixtures of dipalmitoyl phosphatidylcholine and dipalmitoyl phosphatidylethanol, and their resistance to pancreatic phospholipase A 2 catalysed hydrolysis were studied. Three kinds of liposomes with insulin were prepared to examine the pharmacological availability of liposomes with phosphatidylethanol: (i) dipalmitoyl phosphatidylcholine/dipalmitoyl phosphatidylethanol (1:1 w/w) liposomes; (ii) dipalmitoyl phosphatidylcholine/dipalmitoyl phosphatidylethanol/palmitoyl–stearoyl sucrose (1:1:0.2) liposomes; and (iii) liposomes composed of natural phosphatidylcholine and phosphatidylinositol (1:1). The resultant liposomes were orally administrated to rats with blood glucose concentration of 270 mg/100 ml in a dose of 12 IU/kg body weight. Blood samples were collected 0.5, 1.5, 3, 5, and 24 h after treatment. Oral administration of all liposomal species resulted in hyperinsulinemia. Hyperinsulinemia induced by liposomes containing dipalmitoyl phosphatidylethanol was attended by a decrease of blood glucose concentration. No correlation between insulin level and glucose concentration in the rat blood after oral administration of phosphatidylinositol-containing liposomes was observed.