Development and Evaluation of Topical Nano Formulation of Leaf of Adina cordifolia for Wound Healing Activity

Background: Chronic and acute wounds remain a significant clinical challenge due to delayed healing, infection risk, and limitations of conventional topical therapies. The integration of medicinal plant-derived bioactives with nanotechnology offers a promising strategy to enhance wound repair and therapeutic outcomes. Aim: This study aimed to develop and evaluate a novel topical nano-hydrogel formulation containing Adina cordifolia leaf extract-mediated Copper Oxide (CuO) nanoparticles for enhanced wound healing activity. Methods: CuO nanoparticles were synthesised using a green synthesis approach employing A. cordifolia leaf extract and characterised by UV-visible spectroscopy, X-ray Diffraction (XRD), particle size analysis, and zeta potential measurement. The nanoparticles were incorporated into a Carbopol 934-based hydrogel. Formulation optimisation was performed using a central composite design, generating thirteen formulations (HGL1-HGL13). The optimised formulation was evaluated for in vitro drug release kinetics, drug-excipient compatibility, stability, and model validation. In vivo wound healing efficacy was assessed in Wistar rats by monitoring wound contraction and epithelialisation over 15 days. Results: The synthesised CuO nanoparticles showed a mean particle size of 365.3 ± 118.2 nm and a zeta potential of −26.6 mV, indicating good stability. UV-visible spectroscopy (λmax 264 nm) and XRD peaks at 35° and 38° confirmed nanoparticle formation and crystalline nature. Among all formulations, HGL7 exhibited optimal performance with 81% cumulative drug release over 12 h following zero-order kinetics (R2 = 1). Compatibility and validation studies confirmed formulation stability and high predictability (bias < ±1%). In vivo studies demonstrated significantly enhanced wound contraction and epithelialisation in nano-hydrogel-treated animals compared to conventional treatment. Conclusion: The developed A. cordifolia-based CuO nano-hydrogel represents a stable, reproducible, and effective topical formulation that significantly enhances wound healing. This study highlights the potential of combining traditional herbal medicine with nanotechnology for advanced wound care and future clinical and commercial applications. Major Findings: The study developed a stable nano-hydrogel using green-synthesised CuO nanoparticles from A. cordifolia, showing optimal properties and controlled drug release. The optimised formulation (HGL7) significantly accelerated wound contraction and epithelialisation in vivo. These findings demonstrate its strong potential as an effective advanced wound care treatment.