Polymyxin B Nanopreparations Show Promise for Overcoming Drug-Resistant Bacterial Infections, Despite Translational Hurdles

The global rise of multidrug-resistant (MDR) Gram-negative bacterial infections poses a severe public health threat, necessitating novel therapeutic strategies. Polymyxin B, a 'last line of defense' antibiotic, is severely limited by significant dose-dependent nephrotoxicity (up to 50% incidence) and neurotoxicity, alongside the increasing spread of mcr-mediated resistance. Current standard-of-care often struggles to balance efficacy with patient safety, leaving a critical gap for treating these challenging infections. Nanotechnology offers a promising avenue to overcome these limitations by improving drug delivery and reducing systemic exposure.

This comprehensive review systematically summarized the design principles and research progress of Polymyxin B nanopreparations. Researchers analyzed the core issues encountered in their clinical translation, including insufficient biosafety verification, limited targeted delivery efficiency, immature large-scale production technology, and the lack of robust drug resistance prevention and control systems. The review integrated the latest research findings to propose targeted solutions aimed at accelerating the clinical application of these novel antibacterial preparations.

Nanotechnology addresses Polymyxin B's 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. The review highlighted that Polymyxin B's dose-dependent nephrotoxicity, affecting 25-50% of patients, and emerging mcr-mediated resistance are primary drivers for nanopreparation development. Despite promising preclinical data, significant translational hurdles persist, including unclear long-term toxicity mechanisms, poor biofilm penetration, and the absence of standardized quality control. Proposed solutions include optimizing carrier material biocompatibility, constructing intelligent responsive targeting systems, establishing standardized production processes, and developing multi-dimensional drug resistance monitoring strategies. This approach aims to enhance the therapeutic index and overcome resistance.

Polymyxin B nanopreparations leverage targeted delivery and controlled release to mitigate dose-dependent nephrotoxicity (up to 50% incidence) and neurotoxicity, while synergistic co-delivery strategies aim to reverse mcr-mediated bacterial resistance.