Pharmacokinetics and Biodistribution of Phages and their Current Applications in Antimicrobial Therapy

Antimicrobial resistance remains a critical global health concern, necessitating the investigation of alternative therapeutic approaches. With the diminished efficacy of conventional small molecule drugs due to the emergence of highly resilient bacterial strains, there is growing interest in the potential for alternative therapeutic modalities. As naturally occurring viruses of bacteria, bacteriophage (or phage) are being re-envisioned as a platform to engineer properties that can be tailored to target specific bacterial strains and employ diverse antibacterial mechanisms. However, limited understanding of key pharmacological properties of phage is a major challenge to translating its use from preclinical to clinical settings. Here, this work reviews modern advancements in phage-based antimicrobial therapy and discusses the in vivo pharmacokinetics and biodistribution of phage, addressing critical challenges in their application that must be overcome for successful clinical implementation. Given rising antibiotic resistance among pathogens, phage therapy is a possible antimicrobial strategy. Understanding phage pharmacokinetics (PK) and biodistribution (BD) is critical to further development as therapeutic agents. This review summarizes recent advancements in phage therapy and what is currently known about the PK and BD of phages.image