AUTORADIOGRAPHIC IMAGING OF THE DISTRIBUTION OF 5-FLUOROURACIL THROUGH CERVICAL TISSUE FOLLOWING IN-VITRO SURFACE APPLICATION OF A BIOADHESIVE CERVICAL PATCH

The distribution of 5-fluorouracil through cervical tissue has been as sessed following the in vitro application of a bioadhesive patch to ex cised human cervix. The bioadhesive matrix contained a total of 20 mg of 5-fluorouracil spiked with 5-fluorouracil-6-H-3 and was applied for fixed periods of either 4 or 24 hours. Tissue slices were sectioned p erpendicular to the plane of the applied patch and the autoradiographi c image developed by placing a frozen tissue slice on Hyperfilm with s ubsequent instant thawing and refreezing, the resulting bilayer being maintained at -18 degrees C for 24 hours. The developed image was anal ysed by scanning densitometry and raster scans were visualised with th ree-dimensional contouring software. The autoradiograms showed darker areas surrounding tissue ducts, suggesting that 5-FU was spilling from the lumen into the surrounding stroma. Transport of 5FU via aqueous c hannels may thus make an important contribution to the rapid penetrati on of the drug through the cervical stroma. Three-dimensional autoradi ographic images showed that, for a I-hour patch application, there wer e areas of relatively low drug concentration within the upper 5 mm of tissue, where CIN lesions can exist in the glandular tissue or cervica l crypts. However, extending the application time to 24 hours produced areas of high drug concentration extending throughout this region.