Site-Specific Adaptive Milk-Derived Nanovesicles Redefine the Landscape of Oral Insulin Delivery

Overcoming gastrointestinal degradation, epithelial impermeability, and hepatic clearance has been the long-sought goal in oral insulin delivery. Xia et al.’s pioneering work in Science Advances achieves a paradigm shift using site-specific adaptive milk-derived nanovesicles (MiNVs). Engineered from bovine milk exosomes and biothiol-responsive liposomes, MiNVs exploit IgG-FcRn transcytosis for efficient intestinal uptake and glutathione-activated release in the liver. This dual-mechanism enables sustained glycemic control and high oral bioavailability in rodent and porcine diabetic models. More than an incremental advance, this represents a transformative leap toward physiological, injection-free insulin therapy.