Objective

The rapid transit of drug formulations through the stomach and upper small intestine can result in limited absorption, bioavailability and reduced efficacy of a number of drugs. Helicobacter pylori resides in the stomach and resists the frequent gastric emptying, by using a range of outer membrane proteins, called adhesins. These attach onto specific glycan receptors on the gastric epithelium. Only two of those adhesins, BabA and SabA, have been extensively studied. The aim of the present research is to develop a novel gastric-targeted delivery system, which will retain the drug formulation and deliver an incorporated drug in the gastric lumen at a controlled rate, by mimicking the adhesion mechanism of H. pylori. Such a delivery system would be a nanocarrier, surface-modified with the optimal bacterial adhesins. The large-scale expression of LabA in Escherichia coli has been achieved with a yield of 40 mg/L and successful two-step purification (immobilised metal-ion affinity chromatography and size-exclusion chromatography) has produced highly pure protein, appropriate for crystallisation screening, currently being carried out. Differential scanning fluorimetry, circular dichroism spectroscopy and enzyme-linked immunosorbent assay experiments have been carried out for characterisation purposes and X-ray crystallography is planned as soon as sufficient protein crystals are obtained. This research constitutes a general attempt for characterisation an