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, antiinflamma tory drug prednisolone sodium phosphate (PSP) across the epithelial ba rrier. Methods. Microspheres were prepared using a precipitation metho d and loaded with PSP. Transport studies were performed in a diffusion cell chamber using the polarized human cell line HT-29(B6). Porcine s mall intestine and fluorescence-labeled microspheres were used to inve stigate penetration ability of microspheres. Results, It was shown tha t transport of PSP drug solution was not saturable across the cell mon olayers (P = 8.68 +/- 8.24 X 10(-6) cm sec(-1)) and no sodium dependen cy could be established. EGTA treat ment resulted in an increased perm eability (P = 18.69 +/- 1.09 X 10(-6) cm-sec(-1)), After binding of pr ednisolone to chitosan microspheres its cm sec permeability was enhanc ed drastically compared with the drug solution (P = 35.37 +/- 3.21 X 1 0(-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 o f chitosan microspheres was impaired by pH and ion composition of the medium, whereas the effect remained unchanged in cells treated with ba cterial lipopolysaccharides. In vitro incubation of fluorescence-label ed microspheres in the lumen of freshly excised intestine revealed a s ignificant amount of the spheres in the submucosa. Conclusions. Chitos an 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 micr oparticles are able to pass the epithelial layer Their potential benef it under inflammatory conditions like in inflammatory bowel disease, i n order to establish high drug doses at the region of interest, remain s to be shown.