Nanomedicine for phage therapy: Encapsulation strategies for enhanced antimicrobial efficacy

Antibiotic resistance is a growing global health crisis, driving the need for alternative antimicrobial strategies. Phage therapy has re-emerged as a promising approach due to its specificity and ability to evolve against bacterial resistance mechanisms. However, therapeutic implementation is often challenged by factors such as phage stability, immune clearance, and site-specific delivery. Encapsulation technologies offer a potential solution, enhancing phage bioavailability, systemic circulation, and therapeutic action at the infection site. This review explores the latest advancements in phage encapsulation within the context of nanomedicine-based delivery systems, including polymeric nanoparticles, liposomes, hydrogels, nanofibers, and inorganic nanoparticles. Each system is analyzed regarding its impact on phage stability, pharmacokinetics, and host-pathogen interactions, with a particular focus on applications in clinical and preclinical models of phage therapy. Liposomal and polymeric nanoparticle encapsulation enhance phage persistence in systemic circulation and protect them from degradation. Hydrogels and nanofibers improve localized phage delivery for wound healing applications, while inorganic nanoparticles and stimuli-responsive nanocarriers facilitate targeted delivery for intracellular and respiratory infections. By leveraging nanotechnology-driven encapsulation, phage therapy can overcome key delivery challenges, expanding its potential for treating multidrug-resistant bacterial infections. This approach opens new possibilities for precision antimicrobial therapies, reinforcing phage therapy as a viable alternative to conventional antibiotics.