Stomach-specific anti-H. pylori therapy. II. Gastric residence studies of tetracycline-loaded chitosan microspheres in gerbils.

This study examines the gastric residence of chitosan microspheres and the local tetracycline concentrations following oral administration in gerbils. Chitosan microspheres were prepared by ionic cross-linking and precipitation with sodium sulfate. Gastric retention studies were performed by administering radioiodinated [125I] chitosan microsphere suspension in the nonacid-suppressed and acid-suppressed states. At different time points, animals were sacrificed, and the radioactivity in tissues and fluids was measured with a gamma counter. Local tetracycline concentrations were measured using chitosan microspheres loaded with tritiated-[3H]-tetracycline. The radioactivity, measured with a liquid scintillation analyzer, was used to determine the microg of drug per gram of tissues or fluids under nonacid-suppressed and acid-suppressed states. Microspheres with a spherical shape and an average diameter of 2.0-3.0 microm were formed. After 2 hr in the fasted stomach, approximately 10% of the administered dose remained. The microspheres were predominantly found in the colon after 6 hr of administration. There was no detectable radioactivity in the small intestine, plasma, urine, liver, and kidneys. Additionally, acid suppression with ranitidine did not influence the gastric residence time of chitosan microspheres. To our disappointment, tetracycline concentration profile in the stomach from microsphere formulation was similar to the aqueous solution. Also, there was no significant difference between the stomach tetracycline concentrations in the nonacid-suppressed and acid-suppressed states. The drug was predominantly found in the colon and urine samples after 6 hr. Tetracycline could not be detected in the plasma, small intestine, liver, or kidneys. Results of this study show that chitosan microspheres prepared by ionic cross-linking do not provide a longer residence time in the fasted gerbil stomach. The tetracycline concentration profile in the stomach, following administration in microsphere formulation, was similar to that of aqueous solution. Lastly, acid suppression did not influence the gastric residence time of chitosan microspheres or tetracycline concentration profiles.