Synergistic effect of zinc oxide nanoparticles and antibiotics: a strategy to combat bacterial resistance

Abstract Antimicrobial resistance (AMR) continues to compromise the clinical utility of conventional antibiotics, highlighting the need for innovative adjuvant strategies. Zinc oxide nanoparticles (ZnO-NP) have gained attention due to their intrinsic antimicrobial properties and capacity to potentiate antibiotic activity through multimodal mechanisms. This scoping review systematically mapped current evidence on ZnO-NP with antibiotics combinations (ZnO-NP-antibiotic) following the PRISMA-ScR guidelines. Searches in PubMed, Scopus, and Web of Science identified 14 eligible studies. To ensure comprehensive coverage of the literature, an additional manual search was conducted using Google Scholar and the reference lists of the included studies, and 10 further articles were identified. In total, 24 articles are included in this scoping review. Most investigations relied on simple physical mixtures (n = 13); while fewer explored conjugation between ZnO-NP-antibiotic (n = 3); encapsulated systems (n = 4); or drug-loaded (n = 4). Better antimicrobial activity was consistently reported across multiple antibiotic classes. Although all studies evaluated planktonic activity, only 10 incorporated biofilm models. Notably, translational maturity remains limited: more than half of the studies (n = 14) did not include toxicity assessment, and safety evaluation was considered based on in vitro cytotoxicity assays (n = 5); in vivo investigations (n = 5) or Hen's Egg Test—Chorioallantoic Membrane (HET-CAM) (n = 1). These findings indicate that ZnO-NP-antibiotic systems remain predominantly in the early stages of development. Future progress will require standardized antibiofilm methodologies, systematic toxicological profiling, pharmacokinetic characterization, and mechanistic validation to establish reproducible structure–activity relationships. Addressing these translational and regulatory challenges will determine whether nanoparticle-mediated synergy can advance beyond a laboratory proof-of-concept toward clinically viable antimicrobial strategies.