Formulation and Evaluation of Multi-particulate Antibiotic Alternatives for Oral Delivery to Livestock Animals to Target Gut Pathogens

This thesis explored strategies for enhanced oral delivery of antibiotic alternatives to the livestock intestinal tract to target enteric pathogens. The first part dealt with formulating a liquid essential oil (EO) into solidified granules and subsequently enteric coated for intestinal release. Trans-cinnamaldehyde (CIN), a model EO compound with strong antibacterial activity was formulated into granules using a three-component phase-diagram, yielding granules with high loading and stability, and enteric coated by fluid-bed processing. Antibacterial activity of CIN remained intact throughout manufacturing, after addition of 1% eugenol to prevent autoxidation of CIN which lasted for at least 1 year under ambient storage. In animal trials, coated granules delivered CIN in higher concentrations than free oil to the lower intestinal regions where pathogens colonize. The second part explored bacteriophage microencapsulation for oral, bio-control of intestinal Salmonella in chickens. Preliminary studies revealed the phage intestinal distribution and fecal excretion pattern following a single oral dose, and optimized the Ca-alginate-whey protein formulation of microbeads for quicker phage release. Phage lytic activity studies against a target pathogen showed single phages were insufficient at maintaining reduction of STT104NalR, rather phage cocktails were required to maintain reduction in vitro and in animal digesta, which achieved reductions of several log10CFU/g digesta. Two trials were carried out, testing the effectiveness of pathogen reduction by phage cocktails administered to chicks experimentally infected with STDT104NalR. Trial #1 showed that cocktail 1 did not significantly affect the colonization levels even though in vitro activity was good. Trial 2 re-tested CT1 along with an expanded cocktail 2, with larger animal groups. CT1 yielded a similar lack of efficacy, while CT2 achieved significant reductions of STDT104NalR in ileum, ceca, and colon after 7 days, twice-daily administration with feed. This study suggests that phage cocktails microencapsulated for continuous oral administration with feed could reduce intestinal pathogens.Ph.D.2019-02-09 00:00:0