Improving intestinal insulin absorption efficiency through coadministration of cell-penetrating peptide and hydroxypropyl-β-cyclodextrin

The effects of a cell-penetrating peptide (CPP) and hydroxypropyl-β-cyclodextrin (HP-β-CD) on intestinal insulin absorption efficiency were investigated in this study. CPP (R8) and HP-β-CD were added to insulin and the in vitro absorption efficiency in a Caco-2 cell monolayer and in vivo absorption efficiency in diabetic rats were tested. The results showed that the transportation efficiency of insulin-CPP across the Caco-2 cell monolayer was 5–7 times greater and that of insulin–HP-β-CD–CPP (co-treated with HP-β-CD and CPP) was 8–10 times greater than normal insulin. Importantly, these combinations significantly reduced glycemia in diabetic rats. The formulation of insulin–HP-β-CD–CPP showed the highest increase in the permeability of insulin and the best biological response in diabetic rats of all the treatments. This study suggests that coadministration of HP-β-CD and CPP has potential in the development of oral insulin.