LIQUID SCINTILLATION SPECTROMETRY OF 5-FLUOROURACIL IN CERVICAL TISSUE FOLLOWING IN-VITRO SURFACE APPLICATION OF A BIOADHESIVE CERVICAL PATCH

The potential use of bioadhesive technology for the treatment of cervi cal intraepithelial neoplasia was investigated. A cervical patch was d esigned containing 5-fluorouracil in a bioadhesive matrix and polyviny l chloride as the backing layer. The concentration of 5-fluorouracil a t specified tissue depths from the cervical surface was determined in vitro in relation to the ability of the drug to reach precancerous foc i in cervical crypts up to 4 mm below the tissue surface. Thus, tissue was exposed to drug-loaded patches spiked with 5-fluorouracil-6-H-3 a nd subsequently sectioned to obtain tissue slices at different depths. The concentration of 5-fluorouracil was determined by liquid scintill ation spectrometry. Drug penetration into cervical tissue exceeded a d epth of 5.5 mm. Furthermore, the concentration in the tissue depended on the drug loading in the patch. Patches containing 10 and 20 mg of 5 -fluorouracil produced a linear drug gradient that was established aft er a 4 hour application of the patch and persisted over 24 hours. Howe ver, patches containing 3.5 mg of 5-fluorouracil displayed signs of dr ug exhaustion after 24 hours. The penetration characteristics of 5-flu orouracil through cervical tissue using the cervical patch delivery sy stem were sufficiently favourable to warrant further clinical investig ations.