The potential use of poly(methacrylic acid) hydrogels for oral administration of drugs and vaccines to ruminants

Abstract

Poly(methacrylic acid) hydrogels were investigated for the delivery of a model antigen to the lower gastrointestinal tract of sheep. Hydrogels were tested by incorporating a radiopaque material, administering them orally to a sheep, and then radiographing the sheep. The potential for loading high molecular weight proteins into hydrogels was determined by absorbing hydrogels with culture supematants of the bacterium Pasteurella haemolytica. The hydrogels were dried, hydrated, and the culture supematants eluted. The eluents were assayed for the presence of the 102 kDa proteinaceous exotoxin. The hydrogels readily bypassed the first stomach and swelled releasing a radiopaque dye into the lower gastrointestinal tract. Chromium-loaded hydrogels were then administered to a sheep and intestinal contents were collected for 5 days. Chromium was detected in the intestinal contents of the sheep for 96 h with peak levels detected at 12–15 h after administration. Eluents of the hydrogels loaded with culture supematants contained readily detectable amounts of the proteinaceous exotoxin. PMA hydrogels were then absorbed with a vaccine consisting of culture supematants of a pulmonary bacterium P. haemolytica. Hydrogels containing vaccine were administered orally to calves. Calves were challenged by an intrabronchial dose of bacteria. The length of time each calf survived was noted. All surviving calves were killed 3 days post-challenge. A post-mortem examination was performed to evaluate the severity of the pneumonic lesions. Vaccinated calves had less pneumonia and lived longer than control calves. Results of this study indicate that poly (methacrylic acid) hydrogels could be used to administer drugs and proteinaceous vaccines orally to ruminants.