Bacillus-produced surfactin for intranasal delivery of insulin in diabetic mice

Previous studies have shown that Bacillus-produced surfactin (SFN) can be used for oral delivery of insulin (INS). To improve the bioavailability of INS, we determined the effects of SFN on intranasal delivery of INS in diabetic mice. Combinations of SFN and INS at different doses were used for intranasal administration of diabetic mice. The plasma levels of glucose and INS were determined at various time intervals after intranasal administration, and then, the hypoglycemic effects and relative bioavailability of INS were calculated. Glucose tolerance test was performed to determine the effects of intranasal delivery of INS plus SFN on the control of glucose levels. Diabetic mice were also intranasally administered with the INS and SFN combo for 7 days to determine the short-term stability of this formulation for controlling blood glucose levels. A combination of 20 IU/kg INS and 1.6 mg/kg SFN achieved the best hypoglycemic effects for intranasal administration, with a maximal hypoglycemic rate of 29.59% and a maximal blood INS concentration of 45.47 μIU/ml 2 h after administration. As a result, a relatively increased bioavailability of 8.55% was achieved. Glucose tolerance test showed that intranasal delivery of INS plus SFN could effectively control the blood glucose levels after the influx of glucose. Furthermore, intranasal INS plus SFN could be used for controlling blood glucose daily for a short term. Histological evaluation showed no changes in the morphology of the nasal mucosa after exposure to SFN plus INS. SFN is potentially useful for intranasal delivery of INS to control blood glucose levels.