Enhancing the loading and controlled release performance of hyaluronic acid for quercetin via ferrous ion coordination.

This study aimed to prepare Fe2+-quercetin-hyaluronic acid (HA) ternary complexes via a two-step method involving pH-driven assembly and ferrous ion coordination, to enhance the encapsulation, stabilization, and controlled-release characteristics of HA for quercetin (QUE). Results from FT-IR, XRD, XPS, microstructure, and particle size analyses suggested that Fe2+-mediated coordination interactions contributed to the formation of a more compact QUE-HA structure, the QUE-HA binary complexes mainly through coordination, transforming the complexes from large, loose coral-cluster structures into compact, uniform, small-sized nanoparticles. Compared with the binary complexes, Fe2+ coordination significantly increased the encapsulation efficiency of QUE and its photothermal stability, while endowing the carrier with enhanced physical stability (centrifugation, pH, and thermal stability). In vitro release assays showed that Fe2+ coordination reduced the release rate of QUE in neutral environments (Fickian diffusion kinetics) and conferred distinct pH-responsive release behavior (fast release in acidic media, slow release in neutral media). The findings provide a theoretical basis for the development of polysaccharide-based delivery systems for lipophilic polyphenols with high loading efficiency, high stability, and pH-responsive release.