Advancing bacteriophage therapy through encapsulation: An evidence-based scoping review from animal trials

BACKGROUND: The escalating threat of antimicrobial resistance has renewed interest in bacteriophage (phage) therapy, with encapsulation emerging as a promising strategy to enhance phage stability, bioavailability and targeted delivery. OBJECTIVES: To comprehensively map and synthesize the available in vivo evidence on encapsulated phage therapy and identify translational gaps relevant to clinical advancement. METHODS: Following PRISMA-ScR guidelines, we systematically searched Web of Science Core Collection, Cochrane Central, PubMed, MEDLINE (Ovid), and Scopus. RESULTS: Across 56 included studies, research output was concentrated in Asia, particularly India and China. Ionotropic gelation and alginate-based carriers were the most frequently used encapsulation strategies. Oral/gavage administration was the predominant route of phage delivery, with mice and chickens representing the most frequently used animal models. Encapsulated phage demonstrated high encapsulation efficiency, improved survival in simulated gastric fluid, and efficient release in simulated intestinal fluid, with significant therapeutic outcomes reported in 94.6% (53/56) of in vivo studies. CONCLUSION: Encapsulated phage therapy shows promising preclinical efficacy, but translational gaps remain. Future research should prioritize large-animal models, long-term studies, and standardized, scalable encapsulation approaches to support clinical translation and regulatory advancement.