Flavonoid-containing copolymers can act as both extended-release excipients and active pharmaceutical ingredients for the treatment of diabetes

• Natural-based polymers can act as both sustained-release excipients and active pharmaceutical ingredients. • Synthesize three polymers named p(AAPBA- b -Chrysin), p (AAPBA- b -Biochanin A) and p (AAPBA- b -Gardenin B). • The materials have superior slow-release excipients performance, as well as not lost their pharmacological performance. This study focuses on multifaceted applications of plant-based natural products in the treatment of diabetes, specifically aiming to use flavonoids as both active ingredients and extended-release excipients for drug delivery. Three flavonoids (Chrysin, Biochanin A and Gardenin B) were acrylated and subsequently block copolymerised with 3-acrylamido phenyl boronic acid (AAPBA) to yield p(AAPBA- b -Chrysin), p(AAPBA- b -BiochaninA) and p(AAPBA- b -Gardenin B), collectively referred to as p(AAPBA- b -acrylic acid flavone) nanoparticles (NPs). The polymers were next formulated into NPs, and their stability, pH-responsiveness and glucose sensitivity were evaluated. These NPs can be loaded with insulin and have sustained-release properties, with insulin release being accelerated in the presence of glucose. The cytocompatibility of p(AAPBA- b -acrylic acid flavone) NPs was confirmed via cytotoxicity tests in vitro , which revealed that they were mainly accumulated in the liver and kidneys 24 h after injection. In a diabetic mouse model, these NPs were shown to reduce blood sugar levels in the long term; protect liver, kidney and heart function; reduce inflammatory factor levels; and balance oxidative capacity. Therefore, our flavonoid-based NPs can serve as efficient drug delivery systems for the treatment of diabetes.