Orally Administered Liposome-Entrapped Insulin in Diabetic Animals

Abstract

The effects were investigated of liposome-entrapped insulin (LEI) administered orally at 1/2 to 1/10 of previously reported doses, on plasma glucose and insulin in the spontaneously diabetic BB Wistar rat and in alloxan-induced diabetic rabbits. Incorporation of insulin within the liposome fraction ranged from 15-23%. Radioimmunoassay of Triton X-100 treated LEI yielded insulin values in high agreement (82 .+-. 10%) with those predicted based on estimated incorporation. Whereas insulin alone, or liposomes devoid of insulin had no effect, LEI 5 U/kg significantly reduced glucose and raised insulin in 54% of rats (13 of 24) and 67% of the rabbits (6 of 9). Among the rats that responded, blood glucose fell from a basal of 318 .+-. 21 mg/dl to a nadir of 186 .+-. 22 mg/dl at 2 h (P < 0.001); values at 1, 2 and 4 h were all significantly less (58-69%) than basal. Similarly, glucose declined significantly for 3 h post LEI in the rabbits while IRI rose from 30 .+-. 7 .mu.U/ml to a peak of 399 .+-. 75 .mu.U/ml at 1 h (P < 0.001); values at 2 and 3 h remained significantly elevated. Some batches of LEI failed to reduce glucose despite apparently adequate incorporation, while even with effective batches some animals failed to respond. Thus, although orally administered LEI can be effective, their stability and effectiveness are not completely predictable.