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  • bioadhesive  (2)
  • 1
    ISSN: 1573-904X
    Keywords: autoradiography ; bioadhesive ; cervical intraepithelial neoplasia ; 5-fluorouracil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The distribution of 5-fluorouracil through cervical tissue has been assessed following the in vitro application of a bioadhesive patch to excised human cervix. The bioadhesive matrix contained a total of 20 mg of 5-fluorouracil spiked with 5-fluorouracil-6-3H and was applied for fixed periods of either 4 or 24 hours. Tissue slices were sectioned perpendicular to the plane of the applied patch and the autoradiographic image developed by placing a frozen tissue slice on Hyperfilm with subsequent instant thawing and refreezing, the resulting bilayer being maintained at −18°C for 24 hours. The developed image was analysed by scanning densitometry and raster scans were visualised with three-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 channels may thus make an important contribution to the rapid penetration of the drug through the cervical stroma. Three-dimensional autoradiographic images showed that, for a 4-hour patch application, there were areas of relatively low drug concentration within the upper 5 mm of tissue, where CIN lesions can exist in the glandular tissue or cervical crypts. However, extending the application time to 24 hours produced areas of high drug concentration extending throughout this region.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: cervical intraepithelial neoplasia ; bioadhesive ; 5-fluorouracil ; liquid scintillation spectrometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The potential use of bioadhesive technology for the treatment of cervical intraepithelial neoplasia was investigated. A cervical patch was designed containing 5-fluorouracil in a bioadhesive matrix and polyvinyl chloride as the backing layer. The concentration of 5-fluorouracil at specified tissue depths from the cervical surface was determined in vitro in relation to the ability of the drug to reach precancerous foci in cervical crypts up to 4 mm below the tissue surface. Thus, tissue was exposed to drug-loaded patches spiked with 5-fluorouracil-6-3H and subsequently sectioned to obtain tissue slices at different depths. The concentration of 5-fluorouracil was determined by liquid scintillation spectrometry. Drug penetration into cervical tissue exceeded a depth 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 after a 4 hour application of the patch and persisted over 24 hours. However, patches containing 3.5 mg of 5-fluorouracil displayed signs of drug exhaustion after 24 hours. The penetration characteristics of 5-fluorouracil through cervical tissue using the cervical patch delivery system were sufficiently favourable to warrant further clinical investigations.
    Type of Medium: Electronic Resource
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