Sacran-based semi-IPN hydrogel with prolonged drug release from curcumin/chitosan nanoparticle and broad bioactivity

Chronic inflammatory diseases and oxidative stress-related conditions remain challenging to manage due to the poor bioavailability, rapid degradation, and systemic toxicity associated with conventional therapies. Curcumin, a natural polyphenol with potent antioxidant and anti-inflammatory properties, holds therapeutic promise but is limited by poor solubility and instability under physiological conditions. Here, we developed a chemically and physically integrated, semi-interpenetrating network (semi-IPN) hydrogel platform for localized and sustained curcumin oral delivery. The hydrogel is composed of poly (2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS), hyaluronic acid (HA), and the supergiant glycosaminoglycanoid, sacran, forming a highly anionic, viscoelastic, highly hydrated and mechanically robust polyelectrolyte network. Curcumin was pre-encapsulated within chitosan/tripolyphosphate nanoparticles (Cur-CSNPs), which were physically entrapped in the hydrogel to confer hierarchical control over drug diffusion. The composite hydrogel exhibited primarily pH-independent, sustained curcumin release, with enhanced swelling capacity and structural integrity attributed to the synergistic interplay of its macromolecular components. In vitro studies demonstrated potent and sustained antioxidant and antibacterial activities against Staphylococcus aureus and Escherichia coli, along with high cytocompatibility in RAW 264.7 macrophages. This macromolecularly engineered, biofunctional hydrogel presents a promising delivery platform for plant-derived bioactives, combining network design with hierarchical drug encapsulation to address key challenges in inflammation-targeted therapeutics.