Carboxymethyl chitosan-sodium alginate/carboxymethyl cellulose pH-responsive efficient drug-loaded gel for the treatment of inflammatory bowel disease.

Budesonide offers potent anti-inflammatory activity and high first-pass metabolism for oral IBD therapy, but existing dosage forms suffer from gastric leakage and intestinal burst release. pH-responsive hydrogel faces a fundamental trade-off: high crosslinking ensures encapsulation yet suppresses release, whereas low crosslinking permits release but fails in encapsulation. To resolve this, this study moves beyond conventional crosslinking design paradigms by proposing a crosslinking strategy that leverages the synergy between electrostatic interactions of cationic and anionic groups and hydrogen bonding. Using CMCS (-NH₂) with SA and CMC (-COOH), one-step citric acid crosslinking forms a dynamic -NH3+/-COO- electrostatic network, affording high encapsulation and pH-responsive swelling (shrinking in gastric acid, swelling in intestinal fluid). A second physical network, built via hydrogen bonds and hydrophobic interactions, retards drug diffusion to suppress burst release. These functionally decoupled networks act synergistically, offering a promising strategy to overcome the encapsulation-release trade-off. The resulting capsules show relatively low drug leakage at pH 1.2 compared with their drug release at pH 6.8/7.4, where sustained release is achieved, converting "gastric leakage + intestinal burst" into "gastric protection + intestinal sustained release." This platform provides high-encapsulation, controlled-release oral Bud delivery for IBD and establishes a "functional decoupling-synergistic integration" paradigm for smart responsive hydrogel.