Polymeric nano-vesicles via intermolecular action to load and orally deliver insulin with enhanced hypoglycemic effect

Abstract

To date few polymeric vesicles have been investigated to improve oral insulin (INS) absorption due to their limited loading capacity. Therefore, an amphiphilic polyphosphazene (PEOP) containing lipid-like octadecylphosphoethanolamine (OPA) groups and amino-modified poly(ethylene glycol) at the proper ratio was designed and synthesized in this study. It was found that PEOP can self-assemble into nano-vesicles, which displayed considerable loading capability for INS by taking advantage of the synergetic effect of the interaction between OPA and INS and the physical encapsulation by the aqueous lumen of the vesicles. Furthermore, PEOP vesicles can promote INS absorption across the subsequent lymphatic transport of PEOP vesicles after their uptake by the enterocytes in the gastrointestinal tract, and consequently achieve better hypoglycemic effects in vivo. These results suggested that PEOP vesicles have great potential as oral INS carriers for diabetes therapy.