Development and swallowability evaluation of easy-to-swallow anthocyanin-loaded ROS-responsive hydrogels

As a clinically prevalent condition, dysphagia substantially compromises the quality of life of patients and imposes substantial economic burdens on healthcare systems. In this study, a reactive oxygen species (ROS)-responsive cationic liposome and inulin hydrogel composite system was developed to deliver blueberry anthocyanins (ACNs). Mitochondria-targeting ACN-loaded liposomes with triphenylphosphonium (TPP) (TPP-Lip@ACNs) were prepared using the thin-film hydration method, and a hydrogel with 60 % inulin concentration, International Dysphagia Diet Standardisation Initiative (IDDSI) Level 5, was screened as the optimal carrier. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed that TPP-Lip@ACNs had a particle size of 101.5 nm, with structural disintegration under H₂O₂ stimulation due to the cleavage of thioketal (TK) bonds, demonstrating ROS-responsive characteristics. Scanning electron microscopy (SEM) revealed that the inulin hydrogel had a honeycomb-like porous structure, encapsulating liposomes and slowing down drug release, reducing the 12-h cumulative release rate from 90.20 % (free liposomes) to 65.67 %. The IDDSI testing classified the hydrogel as Level 5 (pureed) for safe swallowing. Rheological analysis highlighted the superior viscoelastic and self-healing capabilities of the system. In vitro digestion simulations confirmed the stability of the system in simulated gastric fluid (SGF) and intestinal fluid (SIF), with a triggered controlled release in simulated colon fluid (SCF). Cytotoxicity and hemocompatibility tests showed no significant impact on Caco-2 cell viability and hemolysis rates of <5 %, indicating high biocompatibility. These findings provide a novel strategy for designing functional pigment delivery systems and developing dysphagia-oriented diets.