From Laboratory to Clinic: Translational Medicine Paradigm of Polymyxin B Nanopreparations for Overcoming Drug-Resistant Bacterial Infections

The global prevalence of multidrug-resistant (MDR) Gram-negative bacterial infections has posed a severe threat to public health security. As the “last line of defense” antibiotic against such infections, polymyxin B is severely limited in clinical application by dose-dependent nephrotoxicity (25– 50% incidence), neurotoxicity, and the global spread of mcr-mediated resistance. Nanotechnology overcomes these limitations through three key mechanisms: (1) targeted enrichment at infection sites to reduce systemic exposure; (2) controlled drug release to minimize peak concentration-related toxicity; and (3) synergistic co-delivery to reverse bacterial resistance. This review systematically summarizes the design principles and research progress of polymyxin B nanopreparations, focuses on analyzing the core issues encountered in their clinical translation, including insufficient biosafety verification, limited targeted delivery efficiency, immature large-scale production technology, and lack of drug resistance prevention and control systems. However, these nanopreparations still face critical translational challenges including unclear long-term toxicity mechanisms, poor biofilm penetration, and lack of standardized quality control. Combined with the latest research findings, targeted solutions are proposed, including optimization of carrier material biocompatibility, construction of intelligent responsive targeting systems, establishment of standardized production processes, and development of multi-dimensional drug resistance monitoring strategies. This review aims to provide theoretical support and technical guidance for the clinical translation of polymyxin B nanopreparations, promote their clinical application in the treatment of MDR bacterial infections, and offer a reference paradigm for the development of novel antibacterial preparations.