CYTOTOXICITY OF 5-FLUOROURACIL RELEASED FROM A BIOADHESIVE PATCH INTOUTERINE CERVICAL TISSUE

HeLa cells were used as a model cell line to evaluate the cytotoxic co ncentration of 5-fluorouracil as a candidate drug for the topical trea tment of cervical intraepithelial neoplasia (CIN). Cytotoxicity was me asured by exposing cell suspensions to increasing concentrations of dr ug and measuring the decreased rate of cell growth. Results were confi rmed by photographing monolayers and estimating the ratio of cells ent ering mitosis. A drug concentration of 10(-4) M was found to be cytoto xic. Cervical tissue samples were exposed for either 4 or 24 h periods to 5-fluorouracil released from a bioadhesive cervical patch containi ng 20 mg of drug. The concentration distribution of 5-fluorouracil thr ough cervical tissue were estimated from the amounts, as determined by HPLC, extracted from tissue slices harvested at depths down to 5 mm f rom the surface. Even at this depth, the tissue concentration followin g a 24-h exposure to 5-fluorouracil was 100-fold that of the determine d cytotoxic drug concentration, indicating that the patch delivery sys tem could result in clinically effective drug concentrations in those areas of the cervical stroma where pre-cancerous lesions characteristi c of cervical intraepithelial neoplasia can occur. (C) 1997 Elsevier S cience B.V.