Latest Advances in Inhalable Dry Powder Bacteriophage Therapy for Pulmonary Infections.

The concerning increase in respiratory infections that are resistant to multiple drugs has led to a growing interest in bacteriophage therapy as a potential alternative to conventional antibiotics. Effective phage delivery to the lungs, however, presents several formulation and stability issues, particularly for inhalation-based methods. This review highlights current developments in the creation of dry powder formulations that can be inhaled for pulmonary phage therapy, with a focus on encapsulation methods based on nanoparticles, such as solid lipid nanoparticles (SLNs) and polymer-based nanoparticles. These carriers enhance the aerodynamic characteristics of phages, making them suitable for deep lung deposition, while also protecting them during processing and storage. Several drying methods have been investigated to create powders with optimal morphologies, porosity, and dispersibility, including spray drying and spray freeze drying. The review also emphasizes how the phage morphotype affects stability, especially when nebulization stress is present. Furthermore, the advantages of nanoparticle matrices are confirmed by the reduced viability loss (usually< 0.5 log PFU) of encapsulated phages. Standardizing production processes, scaling up, and ensuring regulatory compliance remain challenging despite encouraging preclinical results. The combination of phage therapy with nanotechnology creates new avenues for the utilization of inhalable delivery methods to treat multidrug-resistant pulmonary infections. To translate these novel formulations from preclinical development to clinical application, sustained multidisciplinary collaboration across pharmaceutical sciences, microbiology, and clinical pharmacology is essential.