Mechanism-guided metal complex therapeutics for biofilm-driven wound infections and transdermal delivery

Chronic wound infections remain a major healthcare challenge due to persistent polymicrobial biofilms and the increasing prevalence of antimicrobial resistance. Conventional antimicrobial therapies often fail to eradicate biofilms, highlighting the need for innovative therapeutic strategies. Metal complexes have emerged as promising candidates owing to their multitarget antimicrobial and antibiofilm activities and potential for localize wound treatment.

This review examines the role of metal complexes in combating biofilm-associated wound infections. Their mechanisms of action, including membrane disruption, redox imbalance, quorum-sensing inhibition, metabolic interference, and biofilm matrix destabilization, are discussed. The review further explores the integration of metal complexes into advanced transdermal and wound patch platforms, including polymeric matrices, nanocomposite systems and stimuli-responsive delivery systems designed to enhance localized drug release, improve wound retention, and minimize systemic toxicity. Current preclinical and translational developments are also highlighted.

Metal-complex-based transdermal therapeutics represent a promising next-generation approach for managing chronic biofilm-mediated wound infections and overcoming antimicrobial resistance. However, successful clinical translation requires addressing challenges related to toxicity, formulation stability, manufacturing scalability, regulatory approval, and long-term safety. Future interdisciplinary efforts integrating microbiology, materials science, and clinical research will be essential to advance these technologies from laboratory to clinical practice.