Bacteriophage purification technologies for advanced clinical translation

The rising rates of antimicrobial resistance (AMR) have become a significant concern, especially as untreatable infections spiral out of control. This has opened new opportunities for developing novel therapeutic approaches. The therapeutic application of phage therapy, utilizing bacteriophages, has gained importance for combating multidrug-resistant (MDR) pathogens, either as an adjuvant or as an alternative to antibiotics. This review evaluates recent advancements in bacteriophage purification technologies in the context of phage therapy against antibiotic resistance, including their modes of action, prospective pharmacology, host ranges, and co-evolution with bacteria. We have also reviewed conventional and emerging bacteriophage purification techniques that aim to enhance the therapeutic potential of bacteriophages, including microfluidics, aqueous two-phase systems, monolithic columns, and chromatography-based membrane systems for endotoxin removal, to improve contaminant removal while maintaining phage infectivity and structural integrity. These modern and efficient purification strategies are being upgraded as a framework towards highly specific, reliable, scalable, and regulatory-compliant purification platforms. Such advancements aim to facilitate the removal of endotoxins, cell debris, and other impurities while preserving phage infectivity and structural integrity. These components are of great importance for the provision and clinical translation of phage therapy, as there is an urgent need for an efficient purification strategy to ensure high-grade purity, safety, and consistency of phage preparations. We also outline the primary associated challenges of phage resistance, immunogenicity, and manufacturing standardization that hinder the development of phage therapy. While there are hurdles to overcome, the use of phages has the potential to form an integrated approach to personalized medicine in addressing antibiotic-resistant strains in the post-antibiotic era.