Construction of naringenin-loaded chitosan/sodium alginate nanocomposite gels and their controlled-release kinetics in simulated gastrointestinal media.

Naringenin has gastrointestinal pharmacological potential, but poor aqueous solubility, rapid crystallization and limited intestinal residence constrain oral formulation performance. This study evaluated whether coupled tripolyphosphate (TPP) and calcium-ion gelation could produce chitosan/sodium alginate (CS/ALG) nanocomposite gels that balance drug loading, gastric protection and intestinal release. Ten independently prepared formulations varied polymer composition, crosslinker density and naringenin feed. The optimized CA-21 formulation had a hydrodynamic diameter of 227.2 ± 9.4 nm, polydispersity index (PDI) of 0.14 ± 0.02, zeta potential of 18.9 ± 4.5 mV, encapsulation efficiency (EE) of 90.5 ± 4.7%, drug loading (DL) of 10.0 ± 1.5% and dried-product yield of 89.3 ± 2.2%. Transmission electron microscopy, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis and rheology indicated compact nanodomains, ionic complexation, attenuated crystalline diffraction and a storage-dominant network. CA-21 limited release to 25.2 ± 1.1% during the 2 h gastric phase and reached 63.2 ± 2.1% at 24 h, whereas the naringenin suspension released 87.5 ± 1.7% and 95.9 ± 1.1%, respectively. Two-way analysis of variance identified significant formulation, time and interaction effects (all p < 0.001), and CA-21 release was best described by the Higuchi model (R 2 = 0.964). CA-21 also retained antioxidant activity, bound 52.2 ± 5.2% mucin and achieved an apparent permeability of 1.32 ± 0.14 × 10-6 cm s-1 while maintaining Caco-2 viability above 95%. Thus, CS/ALG ratio and crosslink density jointly controlled the balance between encapsulation, mucoadhesion and pH-dependent release.