Photothermally triggered double-layer hydrogels containing curcumin-loaded pullulan derivatives for controlled drug delivery and wound healing

Abstract

The development of advanced wound healing materials has garnered significant interest due to their potential to enhance therapeutic outcomes. This study presents a novel double-layer hydrogel system for the controlled release of curcumin under near-infrared (NIR) irradiation. The bottom layer, designed to incorporate curcumin, was formulated using pullulan conjugated with β-cyclodextrin and methacrylate (Pul-βCD-MA) in combination with poly(ethylene glycol) diacrylate (PEGDA). This combination significantly enhances curcumin solubility while improving the mechanical properties of the hydrogel. The top layer, composed of methacrylate-modified pullulan (Pul-MA) and polydopamine, serves as a photothermally responsive layer that converts NIR light into heat. The hydrogels were characterized by their morphology, mechanical properties, and drug release behavior. Upon NIR irradiation, the top-layer temperature increased to 40 °C, facilitating controlled release of curcumin from the bottom layer and yielding a cumulative release of 33 % under NIR, compared with 15 % in the absence of NIR. In vitro cell-migration assays demonstrated significantly enhanced wound closure when curcumin-loaded hydrogels were exposed to NIR irradiation. Biocompatibility with human dermal fibroblasts (HDFs) was confirmed, with no detectable cytotoxicity. This innovative double-layer hydrogel enables externally stimulus-responsive drug release and promotes effective wound healing. These findings position the double-layer hydrogel as a promising platform for advanced wound care with potential applications in controlled drug delivery.