Chitosan-encapsulated bacteriophage cocktail as promising oral delivery system to surpass gastrointestinal infection caused by Klebsiella aerogenes.

Bacteriophages hold promise for combating pathogenic bacteria in the human intestinal tract, but their therapeutic potential is limited by harsh stomach conditions, including low pH and digestive enzymes. This study aimed to develop a natural protective mechanism for orally administering phages to treat gastric infections caused by Klebsiella aerogenes. Results revealed that free phages became inactive at pH 3 without protective measures. Encapsulation within sodium alginate (SA) alone (Bead 1) enabled phage survival at pH 2.5. More notably, Bead 2, consisting of a phage cocktail encapsulated in a chitosan-SA matrix supplemented with honey, casein, and gelatin, demonstrated enhanced survival even at pH 1.5. Phage titers in Bead 2 exhibited a controlled release, with near-complete discharge over 5 h in a simulated intestinal solution at 37 °C, ensuring effective delivery to the intestinal environment. Exposure of K. aerogenes to Bead 2 under these conditions resulted in a maximum reduction of 6.2 log CFU/mL, compared to maximal reductions of 2.8 log CFU/mL for Bead 1 and free phages. This optimized bead-encapsulation method provides a viable, efficient, and cost-effective strategy for delivering functional phages to specifically target intestinal bacteria.