Nanotechnologies for targeted bacteriophage therapy: a review

Antimicrobial resistance is a major health issue that rapidly decreases the number of marketed chemical antibiotics that can cure microbial diseases, calling for alternative solutions. Here we review bacteriophage therapy using nanotechnological delivery with focus on definition and classification, dry powder formation, liposome encapsulation of bacteriophages, hydrogels, electrospinning of phages into nanofibers, and phage emulsions. Dry powder can be done by spray drying and lyophilization. Hydrogels include alginate, polyethylene glycol, polyvinyl glycol, nanocellulose, agarose, hyaluronan and poloxamer. We observed that bacteriophage therapy displays advantages such as self-replicating properties, and minimal disruption to the host microbiota. Recently developed lipid-based nanocarriers, hydrogels, and electrospun core–shell nanofibers have improved phage protection under harsh physiological conditions. Encapsulation using microfluidics-derived nanoemulsions and natural polymers allows for controlled, site-specific phage release and enhanced biofilm penetration. Surface modification using biomimetic coatings and biodegradable materials reduces immunogenicity and extends systemic circulation. Limitations of bacteriophage therapy comprise poor phage stability in physiological conditions, rapid removal by the immune system, limited penetration into biofilms, and the absence of standardized, scalable delivery systems. Clinical studies often focus solely on bacterial reduction while overlooking formulation integrity, delivery efficiency, and pharmacokinetics.