Hydrogen-Bonded Poly(vinyl Alcohol)/Tannic Acid/Quercetin Hydrogels for Localized Controlled Drug Delivery.

Localized drug delivery systems provide an effective approach for achieving sustained drug release and prolonged drug retention at the target site while minimizing systemic exposure. In this study, physically crosslinked poly(vinyl alcohol)/tannic acid/quercetin (PVA/TA/Que) (PTQ) hydrogels were developed through hydrogen-bond-mediated self-assembly without chemical crosslinkers. The effect of TA concentration on hydrogel formation, structural properties, thermal stability, swelling, degradation, and release behavior was systematically investigated. Increasing TA concentration accelerated gelation, increased gel content, and produced denser hydrogel networks with lower porosity, reduced water uptake, slower degradation, and improved thermal stability. FT-IR and XRD analyses confirmed hydrogen-bond interactions between PVA and TA and reduced polymer crystallinity. PT50 exhibited the most favorable physicochemical properties and was selected for further evaluation. TA encapsulation efficiency exceeded 93%. In vitro studies demonstrated sustained and pH-responsive TA release, with only 27.39 ± 1.14% released over 312 h at pH 7.4, while Que showed a faster release profile. Hemocompatibility assays revealed hemolysis values below 2%, and hematological, biochemical, and histopathological analyses following subcutaneous implantation in rats showed no detectable systemic toxicity. Overall, the PTQ hydrogels demonstrated favorable physicochemical properties, controlled release behavior, excellent hemocompatibility, and good in vivo biosafety, indicating their potential for localized delivery of bioactive agents.