Enhanced alginate microspheres as means of oral delivery of bacteriophage for reducing Staphylococcus aureus intestinal carriage

Bacteriophage therapy could provide additional treatment for control of intestinal colonization of microbial pathogens. But, efficacy of its oral application may be reduced by sensitivity of certain phages to the low pH in the stomach. The aim of this study was to develop an improved encapsulation formulation with enhanced acid protection for oral delivery of Staphylococcus aureus phage K. Calcium carbonate microparticles were co-encapsulated with phage K into alginate microspheres and tested their efficacy for improved phage viability under in vitro acidic conditions. Free phage was completely destroyed when exposed to simulated gastric fluid (SGF) of pH 2.5. In contrast, alginate encapsulated phage K had a decrease of only 2.4 log units in viability when incubated for 1 h in SGF at pH 2.5. By adding calcium carbonate as an antacid excipient to the alginate microspheres, the survival of encapsulated phage K in SGF was significantly improved, with only a 0.17 log units reduction after 2 h exposure to SGF at pH 2.5. A number of protective agents including trehalose, sucrose, skim milk, and maltodextrin were also tested and were found to increase the viability of encapsulated phage K when subjected to drying. The protective effects varied with the type and concentration of each incorporated additives. The improved encapsulation formulation increased efficacy of phage K survival when exposed to the simulated gastric condition. Here we tested S. aureus phage K as a model but further improvement of the encapsulation formulation could provide a potential technology for reducing intestinal colonization of other pathogens.