3D printed pectin-chitosan polyelectrolyte hydrogels for controlled gastrointestinal release and colon-targeted delivery.

Polysaccharide-based hydrogels, including pectin (PEC) and chitosan (CS), have been utilized for oral delivery because of their high biocompatibility, low immunogenicity, and stimuli-responsiveness. However, ionically crosslinked hydrogels lack structural stiffness because of their low ionic strength in the harsh digestive environment. In this study, we developed 3D printed hydrogels through polyelectrolyte complexation and ionic gelation with two crosslinkers for adjustable mechanical strength and gastrointestinal stability. To achieve high precision dual droplet-based 3D printing, cellulose nanocrystals (CNCs) nanomaterial solutions mixed with two ionic crosslinkers were utilized as the support biomaterial ink. The PEC-CS and CNCs biomaterial inks had their rheological properties and printability optimized to fabricate freeform and hierarchical structures. Compared with PEC hydrogels, PEC-CS hydrogels exhibited enhanced mechanical strength (2.4-fold) and sustained release (2.0-fold). All hydrogels showed colon-targeted delivery and sustained release owing to the shrink in the stomach and pectinase-triggered degradation in the colon. The hydrogels with three different model drug localizations were 3D printed through variations in drug localization and surface area ratios during the printing process, demonstrating precisely controlled gastrointestinal release. This polysaccharide-based 3D printing system can be applied for personalized oral delivery of diverse biopharmaceuticals to desired locations with controlled release in the gastrointestinal tract.