Biomimetic design of semi-IPN hydrogels containing supergiant glycosaminoglycanoid sacran for controlled berberine...

To address the need for prolonged and targeted administration of cationic therapeutics within the gastrointestinal environment, we developed a proteoglycan-mimetic semi-interpenetrating network (semi-IPN) hydrogel incorporating berberine-chitosan nanoparticles (BBR-CSNPs) into a poly(acrylic acid), the supergiant glycosaminoglycanoid sacran, and chondroitin sulfate matrix. This hierarchical design enables dual-stage release control, enhanced mucosal adhesion, and protection of the drug from premature degradation, making it suitable for oral delivery applications requiring prolonged gastrointestinal residence and sustained release. The hydrogels exhibited higher swelling capacity (14.2 times at pH 7.4; 7.1 times at pH 1.2) while maintaining softness and toughness, attributed to the high molecular weight between cross-linking junctions, likely enhanced by sacran's remarkable water retention and entanglement properties with the PAA network. The hydrogels facilitated pH-controlled berberine release (73 % at pH 7.4; 56 % at pH 1.2), with sacran anions effectively restricting drug diffusion, resulting in potent antioxidant properties (DPPH scavenging up to 72 %, ABTS up to 66 %) and showing effective antibacterial effects (inhibition rates of ∼100 % versus E. coli; >90 % against S.aureus; zone of inhibition diameters of 15.8 ± 0.9 mm and 11.6 ± 1.3 mm, respectively). Furthermore, the hydrogels demonstrated excellent cell compatibility with Raw264.7 cells (viability > 95 % at 24 h and 48 h), owing to the presence of sacran and CHS. Thus, this proteoglycan-mimetic design of semi-IPN hydrogels, incorporating the supergiant glycosaminoglycanoid sacran, proves to be a versatile and effective strategy for controlled cationic drug release.