Hierarchically structured alginate/iota-carrageenan hydrogel beads embedding chitosan microparticles for pH-responsive intestinal delivery of curcumin.

Abstract

Curcumin is a bioactive compound with significant therapeutic potential, yet its clinical application is limited by poor aqueous solubility and low gastrointestinal bioavailability. In this study, a fully polysaccharide-based delivery system was rationally designed using alginate and ι-carrageenan as complementary polyanionic matrices, combined with chitosan microparticles (~1.7 μm) as discrete cationic domains. Hierarchical beads were formed via ionotropic crosslinking with Ca2+ and structurally characterized by spectroscopic, morphological, and interfacial analyses, revealing a compositionally heterogeneous architecture with chitosan microparticles preferentially localized near the bead periphery. This organization directly influenced the system's physicochemical behavior, leading to limited curcumin release under simulated gastric conditions (<20%) and pronounced swelling in simulated intestinal fluid, reaching up to 4755% at 37 °C. In intestinal medium, the beads exhibited a sustained and complete release profile within ~30 h, governed by combined diffusion and polymer relaxation mechanisms. Kinetic modeling confirmed a transition from predominantly Fickian diffusion in acidic conditions to anomalous transport in intestinal environments. These findings demonstrate that hierarchical organization and electrostatic interactions can be strategically engineered to modulate structure-property relationships in multicomponent polysaccharide systems. This work provides insights into the rational design of fully biopolymeric platforms for the controlled oral delivery of hydrophobic bioactive compounds.