Evaluation of the factors influencing stomach-specific delivery of antibacterial agents for Helicobacter pylori infection

Because Helicobacter pylori infection is localized in the gastric mucus lay er and at the mucus layer-epithelial cell interface, we have developed amox ycillin- and metronidazole-containing chitosan microspheres for stomach-spe cific drug delivery. Drug-loaded porous chitosan microspheres were prepared by simultaneous cros slinking and precipitation with sodium tripolyphosphate. The release of ant ibacterial agents into simulated gastric fluid (SGF, pH 1.2), and the stabi lity and permeability through gastric mucin, were examined at 37 degrees C. Because of the high porosity of drug-loaded chitosan microspheres, all the amoxycillin and metronidazole were released in 2 h. High-performance liqui d chromatography assays of the antibacterial agents in SGF at 37 degrees C indicated 40% degradation of amoxycillin after 10 h. Metronidazole was comp letely stable for up to 24 h in SGF. Amoxycillin and metronidazole were hig hly permeable through the gastric mucin gel layer. The results of this study show that acid-stable antibacterial agents, such as metronidazole, that rapidly permeate the gastric mucus layer would be ve ry effective for the complete eradication of H. pylori infection when deliv ered specifically at the site of infection in the stomach.