Tf ligand-receptor-mediated exenatide-Zn²⁺ complex oral-delivery system for penetration enhancement of exenatide.

Safe and effective oral delivery of peptide is a challenge. Here, we used exenatide and zinc ions (Zn) to form a complex to explore a meaningful oral-targeted drug-delivery system. Polyethylene glycol-poly(lactic acid-co-glycolic acid) (PEG-PLGA) was used to prepare nanoparticles (NPs) to escape the degradation caused by gastrointestinal enzymes. Transferrin (Tf) was used as a targeting group. PEG-PLGA-NPs and Tf-modified exenatide-Zn-loaded NPs (Tf-PEG-PLGA-NPs) were uniformly sized spheres according to transmission electron microscopy. The results of pharmacodynamic and pharmacokinetic investigations in vivo were consistent with in vitro studies using Caco-2 cells. Tf enhanced NPs transport in cell-uptake and transmembrane-transport experiments. Our results showed that the relative bioavailability of Tf-exenatide-Zn-NPs was higher than that of exenatide-Zn-NPs. The relative bioavailability of Tf-exenatide-Zn-NPs versus subcutaneous injection of exenatide was 6.45%. This was a preliminary exploration of the oral administration of exenatide, that data from which can be used for future investigations.