Amidated Pectin/Nanocellulose Hybrid Cryogel System with a pH-Responsive Release Profile for Small Intestinal Delivery

Cellulose nanofibers and pectin are promising candidates for polysaccharide-based gel carriers. However, their integration into a structurally modified hybrid gel system has not been extensively investigated. In this study, hybrid cryogels with a pH-responsive release profile favoring small intestinal delivery were prepared by freeze-drying various ratios of anionic nanofibrillar cellulose (aNFC) and amidated pectin (AP). Under acidic conditions, carboxylate protonation reduced intermolecular electrostatic repulsion, promoting the formation of the aNFC/AP hybrid gel network. Increasing the AP content enhanced the mechanical strength of the hydrogels and resulted in larger pore sizes after freeze-drying. The hybrid cryogels prolonged the release of a model drug for up to 20–30 min at pH 3.0, while exhibiting rapid release within 1–2 min when the pH exceeded 6.5, due to gel network collapse. The release behavior was governed by both the porous morphology and the crosslinking density of the cryogel scaffolds. These findings demonstrate that aNFC/AP hybrid cryogels possess a well-defined pH-responsive functional window (pH 6.5–7.0) and hold strong potential as oral drug delivery systems targeting the small intestine.