Since it is known that Helicobacter pylori resides in the gastric mucus layer and at the epithelial cell interface, rationale approach of complete eradication would be to deliver acid-stable antibiotics locally at the site of infection. The specific aims of Phase I are: (1) preparation and characterization of antibiotic-containing chitosan microspheres, (2) optimization of the drug release in vitro, (4) examine the gastric residence time of the formulation, and (5) examine the in vivo efficacy of the antibiotic formulation. Amoxicillin-containing porous chitosan microspheres, formed by spray- drying, will be formulated for stomach-specific delivery. Amoxicillin is known have low minimum inhibitory concentrations against H. pylori in vitro, but fails to eradicate the infection when administered alone in vivo. The release profiles of amoxicillin from the microspheres will be optimized in vitro by adjusting the formulation variables such that all of the drug is released in 2.0 h or less. The gastric residence time of the optimized delivery system after oral administration in mice will be determined by fluorescent staining technique. The antibiotic efficacy will be evaluated in vivo in an H. pylori mice model. This novel drug delivery system will increase the concentration of the drug available at the site of infection and decrease the probability of H. pylori resistance. PROPOSED COMMERCIAL APPLICATIONS: Peptic ulcer disease (PUD) affects as many as 10-15% of the U.S. population. The annual cost of hospitalization and treatment is over $2.0 billion. The cost-of chronic pharmacotherapy is approximately $500 million a year or 12% of the total pharmacy costs. Significant potential for revenue generation exists in the development of a stomach-specific antibiotic delivery system for H. pylori infection
