Smart pH-responsive starch granules as a protective platform for gastrointestinal targeted delivery of ellagic acid: Structural stabilization and controlled release.

Oxidized/cross-linked dual-modified starch granules were developed as a pH-responsive delivery system for ellagic acid (EA). Starch was first oxidized via TEMPO-mediation, followed by STMP cross-linking. Single-oxidized (OS20, OS45) and dual-modified (OCS20, OCS45) starches were systematically compared to native starch. Results showed that oxidation enhanced swelling power (SP) and imparted pH-responsive behavior, while cross-linking stabilized the granules across different pH environments. In vitro digestion tests indicated that both modifications provided superior protection for EA in the gastric phase. Notably, the biphasic Makoid-Banakar (bMB) model best described the release kinetics of OCS20 (R2adj = 0.8363), revealing a unique secondary release phase (n2 = 1.373) triggered by structural collapse. This Super Case II transport mechanism facilitated the targeted and prolonged delivery of EA to the small intestine. These intact modified starch granules represent an effective platform for the protective encapsulation and controlled release of hydrophobic bioactive compounds.