Intestinal unidirectional sustained-release hydrogel patch designed for stable oral delivery of active nutrient...

Stable oral delivery of macromolecules, which easily lose conformation and activity, is far more carrier-demanding than small molecules and a long-standing food science challenge. This study developed a cellulose-based IUSRHP to address this issue. Tests under separate independent conditions showed IUSRHP stayed stable in simulated gastric fluid (pH 3.0) for over 3 h, and achieved unidirectional load release in simulated intestinal fluid (pH 7.2). Its loading capacity (96, 125, 200 mg/piece at 10%, 30%, 50% sodium carboxymethylcellulose (NaCMC)) and thermal stability (glass transition temperature (Tg) from 219 °C to 302 °C) rose with NaCMC content. In the gastrointestinal tract, water permeated the pH-responsive layer, swelling the patch into a 3D hydrogel for unidirectional release of proteins (isoelectric point < 7.2) (release rate tunable via protein negative charge). IUSRHP enhances local effective loads concentration, stability and bioavailability, key for stable oral delivery of food nutrient macromolecules or pharmaceutical active proteins.

The online version contains supplementary material available at 10.1007/s10068-026-02194-w.