(PTFS08-04-26) Alginate Hydrogel Encapsulation Improves Gastrointestinal Retention and Colon Delivery of Tart Cherry Anthocyanins Nanoparticles

Objectives: Anthocyanins (ACNs) from tart cherry juice (TCJ) possess potent anti-inflammatory properties but have limited therapeutic potential due to low bioavailability. Therefore, we developed nanoparticles containing TCJ ACNs (Tnano). Because oral delivery of nanoparticles faces challenges such as gastric degradation and barrier penetration, we designed a colon-targeted delivery system to enhance their effectiveness. Alginate, a seaweed-derived polysaccharide, is stable under acidic conditions, resistant to digestive enzymes, and degradable in the colon. Therefore, we encapsulated Tnano within an alginate shell (Alg-Tnano) to improve their stability and bioavailability in a mouse model.

Methods: Alg-Tnano was prepared using an external gelation method. Tnano suspension containing CaCl₂ (0.5-2% w/v) was dispensed dropwise (1 mL/min) through a 30G needle into stirred sodium alginate (1-3% w/v) to form hydrogel beads, which were then crosslinked in CaCl₂ (up to 1% w/v) and vacuum-dried overnight. For in vivo evaluation, rhodamine (Rh) dye, Rh-labeled nanoparticles (Rnano) and alginate-encapsulated Rnano (Alg-Rnano) were orally administered to fasted C57BL/6 mice. Blood was collected up to 24 h post-gavage, and fluorescence distribution in the gastrointestinal (GI) tract, liver, and adipose tissue was analyzed using IVIS imaging.

Results: Stable spherical Alg-Tnano beads were formed, with the optimized formulation (1% CaCl₂, 3% alginate) producing beads 2-3 mm in diameter. Crosslinking with 1% CaCl₂ increased shell thickness, and the nanostructure of Tnano within the shell was confirmed by SEM. Following oral gavage, free Rh rapidly distributed systemically and accumulated in the liver within 1 h. In contrast, Rnano and Alg-Rnano were largely retained in the GI tract, showing gradual systemic release. By 24 h, Alg-Rnano exhibited greater colon localization than Rnano. Plasma fluorescence showed free Rh peaked at 1 h and declined sharply by 24 h, while Rnano and Alg-Rnano showed sustained release, with Alg-Rnano exhibiting the most prolonged and controlled signal.

Conclusions: Alginate encapsulation improves GI retention and enables sustained nanoparticle release with enhanced colon localization, suggesting a promising strategy for oral delivery of bioactive compounds.

Funding Sources: Funded by USDA AFRI award 2023-67017-39555