Work

Formulation, stability, and delivery of bacteriophage cocktails in veterinary medicine: a review of physicochemical constraints and therapeutic outcomes in production animals

Year: 2026

Type: review

Abstract: Intensive food animal production is at risk due to the ever-increasing antimicrobial resistance (AMR) of veterinary pathogens, and it is time to look at alternatives to antibiotics. Bacteriophage (phage) cocktails, which involve the use of several bacteriophages with different host ranges and resistance profiles, are a new and exciting biologic approach. Nevertheless, there are significant physicochemical barriers in the animal host and during feed processing that hinder the translation of promising in vitro bacteriolysis to consistent in vivo therapeutic efficacy. The review critically addresses the interrelated issues of gastric acidity, enzymatic digestion, exposure to bile salts, thermal stress during feed pelleting and osmotic fluctuations, which all contribute to the destruction of orally administered phage titers. We systematically examine formulation technologies such as lyophilization, spray-drying, and alginate, chitosan, lipid nanoparticles and hydrogel encapsulation to protect phages from these destructive environments. When comparing the delivery routes of oral, parenteral, intramammary and aerosol, it is observed that each route places different priorities on biopharmaceutical requirements. Critical evaluation of therapeutic outcomes in poultry, swine, ruminants, and aquaculture has shown that the use of formulations optimized for the gastrointestinal physiology of the target species can lead to significantly reduced target bacterial loads and mortality rates, but failures often occur when in vitro stability data is not supported by an understanding of the pharmacokinetic parameters. For ruminants, there is a remarkable difference between the success of acid-resistant encapsulation in monogastrics and the inability of such methods to work in ruminants due to premature release and inactivation of phages by the forestomach microbiome. We emphasize the need for standardized assays of phage titer in different laboratories, well-defined regulatory processes, and physiologically-based pharmacokinetic/pharmacodynamic models that can predict the temporal and spatial dynamics of phage-bacteria interactions in vivo . This synthesis provides a roadmap for the rational design of phage cocktail products that can reliably reduce antibiotic dependence in veterinary medicine.

Source: Frontiers in Veterinary Science

DOI: 10.3389/fvets.2026.1988130