Inclusion complex based on N-acetyl-L-cysteine and arginine modified hydroxypropyl-β-cyclodextrin for oral insulin...

Insulin is the most effective drug in the treatment of diabetes mellitus. At present, subcutaneous injection is still the common way for insulin delivery. However, oral delivery is considered as the most preferred way for its high patient compliance and the minimal invasiveness. In this study, a novel N-acetyl-L-cysteine and arginine modified hydroxypropyl-β-cyclodextrin (NAC-HP-β-CD-Arg) was successfully synthesized and characterized. The polymer was used as a carrier for oral delivery of insulin by forming NAC-HP-β-CD-Arg@insulin complex. Enzymatic degradation study indicated that the NAC-HP-β-CD-Arg could protect insulin from enzymolysis. Moreover, the polymer exhibited strong binding ability with mucin. The transportation efficiency of NAC-HP-β-CD-Arg@insulin across the Caco-2 cell monolayer was much greater than free insulin. The in vivo study demonstrated that the orally administered NAC-HP-β-CD-Arg@insulin exhibited an excellent and sustained hypoglycemic effect in diabetic rats. It can be concluded that the NAC-HP-β-CD-Arg is a potential carrier for oral delivery of insulin.