Newly designed curcumin-loaded hybrid nanoparticles: a multifunctional strategy for combating oxidative stress, inflammation, and infections to accelerate wound healing and tissue regeneration.

Effective treatment of skin wounds remains a clinical challenge owing to factors such as microbial infections, impaired fibroblast activity, disrupted angiogenesis, and collagen remodeling. In this study, we developed and evaluated novel curcumin-cyclodextrin hybrid nanoparticles (Cur/CD-HNPs) as a multifunctional platform for enhanced wound healing. Nanoparticles (NPs) were prepared via nanoprecipitation. Physicochemical and structural properties were systematically characterized by determining the encapsulation efficiency (EE), particle size, zeta potential, X-XRD, FTIR, SEM, in vitro release, and stability studies. The optimized Cur/CD-HNPs demonstrated a uniform particle size of 150.5 ± 2.8 nm, a surface charge of - 18.5 ± 0.59 mV, a PDI of 0.20 ± 0.03, and a high EE (90.2 ± 2.35%). Cur/CD-HNPs exhibited potent anti-inflammatory effects (97.93 ± 1.24% inhibition of protein denaturation), full antioxidant activity (100% ABTS radical scavenging, IC50 = 12.85 µg/mL), and broad-spectrum antibacterial efficacy. Cur/CD-HNPs exhibited a sustained biphasic release profile, with ~ 82% of Cur released over 24 h, supporting sustained delivery for wound healing applications. In vitro scratch assays revealed enhanced fibroblast proliferation and migration. For in vivo evaluation, the nanoparticles were incorporated into a hydrogel base and applied topically in a rat burn wound model, resulting in significantly accelerated wound closure (P < 0.05). Histopathological examination revealed improved epithelialization, collagen deposition, and tissue regeneration compared with the control groups. Our findings presented Cur/CD-HNPs as a promising therapeutic approach, offering Cur enhanced bioactivity, stability, and regenerative potential. This formulation addresses the key limitations of curcumin and presents a multifunctional and strong translational platform for clinical wound care.