pH-Responsive Sodium Alginate/Carboxymethyl Cellulose Hydrogels for Enhanced Stability and Gastrointestinal Sustained Release Delivery of Chlorogenic Acid

Chlorogenic acid (CGA) is a natural polyphenol with various biological activities, but its poor stability and premature release in the gastrointestinal tract limit oral application. Herein, a pH-responsive bilayer hydrogel based on sodium alginate (SA) and carboxymethyl cellulose (CMC) was developed to enhance the gastrointestinal stability and controlled release of CGA. CGA-loaded SA hydrogels were prepared via Ca2+-induced ionotropic gelation, followed by CMC coating to form a bilayer structure. The SA/CMC hydrogels showed a drug loading capacity of 15.2–16.7% and pH-dependent swelling behavior. In vitro release studies revealed that the bilayer hydrogel suppressed CGA release in simulated gastric fluid (pH 1.2), with a cumulative release of approximately 30%, while enabling sustained release in simulated intestinal fluid (pH 6.8), reaching about 70% within 10 h. Release kinetics indicated that CGA release was controlled by Fickian diffusion under acidic conditions and by a diffusion-polymer relaxation mechanism under intestinal conditions. Moreover, encapsulation in the SA/CMC hydrogel improved the thermal, light, and pH stability of CGA while maintaining its antioxidant activity and biocompatibility. These results indicate that SA/CMC bilayer hydrogels provide a promising strategy for stabilized gastrointestinal delivery of chlorogenic acid.