Synergistic potential of clindamycin hydrochloride loaded on zinc oxide nanoparticles: A novel approach to combat multidrug-resistant infections

The emergence of antimicrobial resistance (AMR) presents a critical challenge to global health, necessitating novel strategies to enhance the efficacy of existing antibiotics. This study investigated the potential of combining zinc oxide nanoparticles (ZnO NPs) with clindamycin to overcome bacterial resistance and improve treatment outcomes. Thus, the loading of clindamycin into ZnO nanoparticles was achieved using varying drug-to-nanocarrier ratios (1:20, 1:10, 1:5), and the formulations were characterized for loading efficiency, particle size, and zeta potential. As well as the antimicrobial assessment of zinc oxide nanoparticles, clindamycin drug and the drug loaded onto ZnO NPs was evaluated against resistant Gram-positive, Gram negative bacterial and one fungal species (Candida albicans). The results revealed a significant increase in drug loading efficiency with optimized nanoparticle formulations. Furthermore, in vitro release studies showed that ZnO NPs provided sustained drug release, offering a controlled and prolonged therapeutic effect. It was concluded that the combination of ZnO NPs and clindamycin demonstrates significant promise for addressing the challenges posed by AMR, indicated by lower the values of both MIC and MBC as well increasing the inhibition zone diameter, providing an innovative and efficient solution for the treatment of several infections, particularly those exhibiting drug resistance profile. The cytotoxicity of ZnO nanoparticles (ZnO NPs), clindamycin, and their nanocomposite was tested in human gingival fibroblasts. The CC₅₀ values were 227.56 µg/mL for the nanocomposite, 154.91 µg/mL for clindamycin, and 106.46 µg/mL for ZnO NPs. Loading of clindamycin in ZnO NPs significantly enhanced its biocompatibility toward human gingival fibroblasts, indicating a safer drug delivery profile with potential synergistic effects. This nanocomposite holds promise for more effective bacterial treatment and overcoming antibiotic resistance. Moreover, this study presents a theoretical investigation into the adsorption of clindamycin (CLA) on ZnO NPs using advanced quantum mechanical methods. Two distinct configurations were identified, each with unique interaction modes and binding energies. Local Energy Decomposition (LED) analysis provided a chemically meaningful breakdown of binding interactions, highlighting the interplay between geometry preparation and interaction energies. The findings of the study offer valuable insights for optimizing nanoparticle-drug interactions, with potential applications in drug delivery and nanotechnology.