The entrapment of biological active substances into liposomes. II. Effects of oral administration of liposomally entrapped insulin in normal and alloxanized rats.
Insulin (I) was entrapped into liposomes of various lipid compositions. After oral administration, some of the normal rats treated with neutral liposomes (c) and (d) having egg yolk lecithin, prepared with 2 or 4 mg I/ml respectively, showed a decrease in blood glucose at 2 and 4 hrs. In alloxanized rats (75 mg alloxan/kg body weight) the positive liposomes (f) have induced in some animals a decrease in blood glucose at both time intervals after oral treatment. When neutral liposomes (c) were administered to diabetic rats (125 mg alloxan/kg body) the blood glucose decreased in 9 of 12 animals from 391 to 125 mg/100 ml blood, at 3 hrs after oral treatment. At 1 h, the effect had appeared in 3 of 14 animals. The neutral liposomes (g) having synthetic lecithin, induced a decrease in blood glucose in 5 of 10 animals. A good correlation was observed between decreased glucose and increased insulin levels with the same variability throughout the treated group. No increased insulin levels were observed in diabetic control and normal rats. By the RIA method, the insulin entrapment was 8%. Histological studies have shown that at 35 min after oral administration, neutral liposomes (c) penetrate deeply into the intestinal wall of alloxanized rats as compared both to the neutral liposomes with synthetic lecithin (g) or to the positive ones (f).