Orally administered dual-responsive insulin nanomedicine for diabetes and diabetic retinopathy

Abstract Diabetic retinopathy (DR), a major ocular complication of diabetes mellitus, remains a leading cause of global vision loss and blindness. Pathological hallmarks of DR include sustained hyperglycemia and elevated oxidative stress. To address these challenges, this study synthesized a dual-responsive nanomaterial (NPS EB ) capable of reacting to reactive oxygen species (ROS) and glucose. NPS EB was co-encapsulated with the anti-inflammatory and antioxidant essential oil from Fructus Alpiniae zerumbet (EOFAZ) and insulin, forming the dual-drug nanocomplex designated NPS EB @EOFAZ/insulin (termed N-EI). The protective properties of this nanomaterial conferred gastrointestinal stability to N-EI. Oral administration of N-EI significantly reduced blood glucose levels in diabetic mice within 6 h while simultaneously alleviating oxidative stress and systemic inflammation. Crucially, N-EI mitigated oxidative stress and inflammatory responses in Müller cells, thereby delaying DR progression. This orally administered, biocompatible dual-responsive nanocomplex demonstrates therapeutic potential for glycemic control and retardation of DR complications, suggesting a novel avenue for oral insulin nanomedicine development.