Oral delivery system for low molecular weight protamine-dextran-poly(lactic-co-glycolic acid) carrying exenatide to overcome the mucus barrier and improve intestinal targeting efficiency.

This study aimed to explore the effect of nanoparticles loaded with exenatide in overcoming the mucus barrier and improving intestinal targeting efficiency, to improve the oral bioavailability. Low molecular weight protamine (LMWP)-dextran-poly(lactic-co-glycolic acid) was used to create LMWP-dextran-poly(lactic-co-glycolic acid)-nanoparticles (LDPs) encapsulating exenatide-Zn complex. LDPs showed improved penetration of the mucus barrier, and LMWP was helpful for mediating cell translocation through protein transduction domains. The absorption sites and distribution rates of LDPs were verified by intestinal localization experiments and distribution experiments. Cell uptake and transmembrane experiments confirmed the absorption efficiency in the intestinal epithelium. Furthermore, the relative bioavailability after oral administration of exenatide-Zn-LDPs was 8.4%, with a significant hypoglycemic effect on Type 2 diabetic mice.