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 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.
Woolfson
A D
AD
School of Pharmacy, Queen's University of Belfast, United Kingdom.
McCafferty
D F
DF
McCarron
P A
PA
Price
J H
JH
D000269:Adhesives; D002584:Cervix Uteri / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D006801:Humans; D012588:Scintillation Counting; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy*
D000269:Adhesives; D005472:Fluorouracil