A pH-stimulated responsive micro-drug delivery system loaded with gastrodin that improves type 2 diabetes

Abstract

Type 2 diabetes mellitus (T2DM) is a rapidly increasing global metabolic disease. The development of effective oral hypoglycemic agents, primarily derived from natural compounds, remains a significant challenge. In this study, we developed pH-responsive sodium alginate (SA) microspheres combined with low methoxy pectin (LMP) that are loaded with gastrodin (Gas) (denoted as Gas@MPs) and successfully delivered Gas to the gut for controlled release. Our in vitro research results indicate that Gas can effectively escape from cellular lysosomes into the cytoplasm, be efficiently absorbed by cells, and exhibit remarkable antioxidant properties. Furthermore, in vitro simulations demonstrated that Gas@MPs effectively prevents gastric juice from interfering with intestinal fluid release. Importantly, Gas@MPs significantly improved the regulation of blood glucose levels and restored impaired islet function in STZ-induced diabetic mice. Additionally, Gas@MPs effectively mitigated insulin resistance and promoted glycogen synthesis by modulating the expression of proteins related to GSK3-β, Nrf2, HO-1, Glut2, and IRS-1 in the pancreatic tissue of diabetic mice. Notably, Gas@MPs also effectively reversed the dysregulation of the gut microenvironment. In conclusion, our research suggests that the oral administration of Gas@MPs represents a promising strategy for alleviating T2DM symptoms and offers new insights into the development of innovative oral natural hypoglycemic agents for the treatment of T2DM.