Selective adhesion of nanoparticles to inflamed tissue in gastric ulcers.

PURPOSE

Gastrointestinal deposition of nanoparticles was examined after oral administration to mice suffering from an experimental gastric ulcer model. Local drug delivery could reduce side effects and would be a distinct improvement compared to existing therapeutic approaches, e.g. in the local therapy of Helicobacter pylori.

METHODS

A gastric ulcer was induced to Swiss mice by acetic acid injection. Fluorescent polystyrene particles with a nominal size of 50, 200, and 750 nm were administered orally for 3 or 5 days and particle adhesion in the gastrointestinal tract analyzed.

RESULTS

In the ulcerated regions, an enhanced particle adhesion was observed compared to healthy controls. A size dependency of the deposition was found which further increased with a prolonged treatment period. For 750 nm particles only fair adhesion was observed (control, 2.0 +/- 1.4%; ulcer, 4.5 +/- 0.7% of daily administered particle mass), while already 200 nm particles showed higher binding (control, 2.9 +/- 1.3%; ulcer, 7.8 +/- 1.2%). Highest relative adhesion was found for 50 nm particles (control, 2.8 +/- 1.3%; ulcer, 10.0 +/- 1.5%). The targeting index of gastric ulcer versus healthy control was nearly constant around 2 after 3 days treatment, but increased distinctly for smaller particles after 5 days.

CONCLUSIONS

The use of sub-micron sized carriers holds promise for the targeted delivery of drugs to the ulcerated mucosal areas in the stomach.