Hypoglycemic effect of intranasally delivered insulin improved with coadministrated novel cell-penetrating peptides

Latroeggtoxin-VI (LETX-VI) was previously shown to cross cell membrane and its C-terminal sequence is the functional peptide segment (FPS) for the transmembrane action. This proof-of-concept study aimed to confirm the promoting-effect of FPS as well as LETX-VI on nasal insulin absorption.

After FPS and LETX-VI were intranasally coadministrated with insulin to mice, respectively, the changes in hypoglycemic effect of the insulin were determined.

Compared with insulin alone, the mixture of insulin and 0.5 mM LETX-VI decreased the peak blood glucose concentration by 33.14% (P < .05); coadministration of insulin and 4 mM FPS decreased the peak value of blood glucose by 19.88% (P < .05). Besides, addition of 4 mM FPS decreased the AUC0-90 min value from 1062.50 of insulin alone to 926.17, which was significantly lower than that of the blank control (P < .05); FPS made the insulin exert hypoglycemic effect earlier and did not change the end time of the hypoglycemic action.

Both LETX-VI and FPS are able to efficiently facilitate nasal insulin absorption and thus enhance the hopyglycemic effect of insulin. Relatively, FPS has a much smaller molecular weight and thus is more promising in the transmembrane delivery of drugs including insulin.