Effects of Gastrointestinal Administration of Human Insulin and a Human Insulin-Deae-Dextran Complex Entrapped in Different Compound Liposomes on Blood Glucose in Rats

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Abstract
The effects of gastrointestinal administration (oral, in duodenum and colon) of human insulin and a human insulin-DEAE (diethylaminoethyl) dextran complex entrapped in different compound liposomes in comparing to human insulin alone given subcutaneously on blood glucose level of normal and STZ-diabetic rats were investigated. The liposomes were prepared from a hydrogenated soy lecithin (Epikuron, E 200 H) and by a high pressure homogenization procedure. Samples were lyophilized and reconstituted in 0.067 M phosphate buffer, pH 7.4 before application. The complexed insulin (0.25 and 0.5 IU/kg insulin) showed no diffrences in blood glucose lowering profiles from the free insulin when both were administered intravenously in normal rats. When given orally, the complex (30 and 60 IU/kg Insulin) entrapped in positive liposomes (E 200 H/cholesterol/stearylamine = 7:2:1, in a molar ratio) indicated no effects in STZ rats. However, this complex liposome (6.0 IU/kg insulin) gave a retention effect of blood glucose lowering as % initial level of about 12% after 5 hours when injected in duodenum and showed two maximum effects of 21 and 22% at 100 and 300 minutes respectively when administered in colon of normal rats. When the free insulin entrapped in positive liposomes was given in duodenum In normal rats, the maximum effect of blood glucose lowering of 10% was observed at 2 hours (6 IU/kg insulin) and 1 hour (12 IU/kg insulin). For the free insulin (12 IU/kg) entrapped in other liposome systems given in duodenum of normal rats, both negative (E 200 H/cholesterol/dlcetyl phosphate=7:2:1, in a molar ratio) and neutral (E 200 H/cholesterol=1:1, in a molar ratio) liposomes indicated the maximum effect of about 30% at 120 minutes. Both cholesterol rich positive (E 200 H/cholesterol/stearylamlne=7:7:1, in a molar ratio) and negative (E 200 H/cholesterol/dicetyl phosphate=7:7:1, in a molar ratio) liposomes showed not only a maximum effect of about 20% at 2 hours, but also a retention of glucose lowering of 20% after 7 hours as well. This study suggested that a development of human Insulin by complexlng with the DEAE-dextran polymer and/or entrapping in liposomes, as a drug delivery system in duodenum and colon, is possible.