Fabrication of Zinc Oxide Nanoparticles Encapsulated Locust Bean Gum for Wound Healing: In Vitro/In Vivo and Molecular Docking Approach

Background: Hydrogel membranes are highly effective biomaterials with huge potential for advanced wound management, offering the dual advantage of maintaining a beneficial moist environment while serving as a localized reservoir for antibacterial agents. Zinc oxide nanoparticles (ZnO NPs) are particularly notable in this regard, possessing potent antibacterial capabilities and intrinsic tissue-healing properties. Methods: In this study, we report the successful fabrication of a novel locust bean gum (LBG) hydrogel encapsulated with ZnO NPs, utilizing AlCl3 as a cross-linking agent. The synthesized nanocomposite hydrogels were structurally and chemically characterized using Scanning Electron Microscopy (SEM) and Fourier-Transform Infrared Spectroscopy (FTIR) followed by in vivo studies using experimental animals by creating wound model. Results: Physicochemical evaluations revealed a concentration and pH-dependent swelling profile, achieving a maximum swelling capacity of 97% at pH 9. In vitro kinetic studies depicted a highly desirable initial burst release of the active therapeutic, subsequently followed by a continuous, sustained release phase that was strictly governed by non-Fickian diffusion mechanics. Furthermore, the optimized formulations achieved excellent entrapment efficiencies (>95%) and substantial free-radical scavenging antioxidant potential (>86%). Biological assessments confirmed the safety and efficacy of the nanocomposites. The formulations exhibited zero cellular toxicity against fibroblast cell lines and demonstrated complete biocompatibility during tissue histopathological evaluations. Significant antimicrobial activity was also observed, as demonstrated by reduction in the Minimum Inhibitory Concentration (MIC) against critical pathogens, including S. aureus, E. coli, P. aeruginosa, and resistant MRSA strains. Crucially, in vivo studies using experimental animal models demonstrated accelerated tissue remodeling, achieving complete wound healing by day 11 and vastly outperforming the control groups. Finally, in silico molecular docking simulations corroborated these empirical findings, revealing strong and favorable binding interactions of the nanocomposite with key target proteins to elucidate its underlying antibacterial mechanisms. Conclusions: Collectively, these results establish the ZnO-loaded LBG hydrogel as a safe, multifunctional, and highly efficient topical drug delivery platform for cutaneous wound healing.