Influence of chitosan microspheres on the transport of prednisolone sodium phosphate across HT-29 cell monolayers.

Purpose: The present study was performed to investigate the influence of chitosan microspheres on transport of the hydrophilic, antiinflammatory drug prednisolone sodium phosphate (PSP) across the epithelial barrier.

Methods: Microspheres were prepared using a precipitation method and loaded with PSP. Transport studies were performed in a diffusion cell chamber using the polarized human cell line HT-29B6. Porcine small intestine and fluorescence-labeled microspheres were used to investigate penetration ability of microspheres.

Results: It was shown that transport of PSP drug solution was not saturable across the cell monolayers (P = 8.68 +/- 8.24 x 10(-6) cm sec-1) and no sodium dependency could be established. EGTA treatment resulted in an increased permeability (P = 18.69 +/- 1.09 x 10(-6) cm sec-1). After binding of prednisolone to chitosan microspheres its permeability was enhanced drastically compared with the drug solution (P = 35.37 +/- 3.21 x 10(-6) cm sec-1). This effect was prevented by EGTA treatment (P = 15.11 +/- 2.57 x 10(-6) cm sec-1). Furthermore the supporting effect of chitosan microspheres was impaired by pH and ion composition of the medium, whereas the effect remained unchanged in cells treated with bacterial lipopolysaccharides. In vitro incubation of fluorescence-labeled microspheres in the lumen of freshly excised intestine revealed a significant amount of the spheres in the submucosa.

Conclusions: Chitosan microspheres are a useful tool to improve the uptake of hydrophilic substances like PSP across epithelial layers. The effect is dependent on the integrity of the intercellular cell contact zones and the microparticles are able to pass the epithelial layer. Their potential benefit under inflammatory conditions like in inflammatory bowel disease, in order to establish high drug doses at the region of interest, remains to be shown.