Cytotoxicity of 5-fluorouracil released from a bioadhesive patch into uterine cervical tissue

Paul McCarron, A. D. Woolfson, D. F. McCafferty, J. H. Price, H. Sidhu, G. I. Hickey

Research output: Contribution to journalArticle

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Abstract

HeLa cells were used as a model cell line to evaluate the cytotoxic concentration of 5-fluorouracil as a candidate drug for the topical treatment of cervical intraepithelial neoplasia (CIN). Cytotoxicity was measured by exposing cell suspensions to increasing concentrations of drug and measuring the decreased rate of cell growth. Results were confirmed by photographing monolayers and estimating the ratio of cells entering mitosis. A drug concentration of 10(-4) M was found to be cytotoxic. Cervical tissue samples were exposed for either 4 or 24 h periods to 5-fluorouracil released from a bioadhesive cervical patch containing 20 mg of drug. The concentration distribution of 5-fluorouracil through cervical tissue were estimated from the amounts, as determined by HPLC, extracted from tissue slices harvested at depths down to 5 mm from the surface. Even at this depth, the tissue concentration following a 24-h exposure to 5-fluorouracil was 100-fold that of the determined cytotoxic drug concentration, indicating that the patch delivery system could result in clinically effective drug concentrations in those areas of the cervical stroma where pre-cancerous lesions characteristic of cervical intraepithelial neoplasia can occur. (C) 1997 Elsevier Science B.V.
LanguageEnglish
Pages69-74
JournalInternational Journal of Pharmaceutics
Volume151
Issue number1
Publication statusPublished - 1997

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Fluorouracil
Pharmaceutical Preparations
Cervical Intraepithelial Neoplasia
HeLa Cells
Mitosis
Suspensions
High Pressure Liquid Chromatography
Cell Line
Growth

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McCarron, P., Woolfson, A. D., McCafferty, D. F., Price, J. H., Sidhu, H., & Hickey, G. I. (1997). Cytotoxicity of 5-fluorouracil released from a bioadhesive patch into uterine cervical tissue. 151(1), 69-74.
McCarron, Paul ; Woolfson, A. D. ; McCafferty, D. F. ; Price, J. H. ; Sidhu, H. ; Hickey, G. I. / Cytotoxicity of 5-fluorouracil released from a bioadhesive patch into uterine cervical tissue. 1997 ; Vol. 151, No. 1. pp. 69-74.
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McCarron, P, Woolfson, AD, McCafferty, DF, Price, JH, Sidhu, H & Hickey, GI 1997, 'Cytotoxicity of 5-fluorouracil released from a bioadhesive patch into uterine cervical tissue', vol. 151, no. 1, pp. 69-74.

Cytotoxicity of 5-fluorouracil released from a bioadhesive patch into uterine cervical tissue. / McCarron, Paul; Woolfson, A. D.; McCafferty, D. F.; Price, J. H.; Sidhu, H.; Hickey, G. I.

Vol. 151, No. 1, 1997, p. 69-74.

Research output: Contribution to journalArticle

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AU - Woolfson, A. D.

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N2 - HeLa cells were used as a model cell line to evaluate the cytotoxic concentration of 5-fluorouracil as a candidate drug for the topical treatment of cervical intraepithelial neoplasia (CIN). Cytotoxicity was measured by exposing cell suspensions to increasing concentrations of drug and measuring the decreased rate of cell growth. Results were confirmed by photographing monolayers and estimating the ratio of cells entering mitosis. A drug concentration of 10(-4) M was found to be cytotoxic. Cervical tissue samples were exposed for either 4 or 24 h periods to 5-fluorouracil released from a bioadhesive cervical patch containing 20 mg of drug. The concentration distribution of 5-fluorouracil through cervical tissue were estimated from the amounts, as determined by HPLC, extracted from tissue slices harvested at depths down to 5 mm from the surface. Even at this depth, the tissue concentration following a 24-h exposure to 5-fluorouracil was 100-fold that of the determined cytotoxic drug concentration, indicating that the patch delivery system could result in clinically effective drug concentrations in those areas of the cervical stroma where pre-cancerous lesions characteristic of cervical intraepithelial neoplasia can occur. (C) 1997 Elsevier Science B.V.

AB - HeLa cells were used as a model cell line to evaluate the cytotoxic concentration of 5-fluorouracil as a candidate drug for the topical treatment of cervical intraepithelial neoplasia (CIN). Cytotoxicity was measured by exposing cell suspensions to increasing concentrations of drug and measuring the decreased rate of cell growth. Results were confirmed by photographing monolayers and estimating the ratio of cells entering mitosis. A drug concentration of 10(-4) M was found to be cytotoxic. Cervical tissue samples were exposed for either 4 or 24 h periods to 5-fluorouracil released from a bioadhesive cervical patch containing 20 mg of drug. The concentration distribution of 5-fluorouracil through cervical tissue were estimated from the amounts, as determined by HPLC, extracted from tissue slices harvested at depths down to 5 mm from the surface. Even at this depth, the tissue concentration following a 24-h exposure to 5-fluorouracil was 100-fold that of the determined cytotoxic drug concentration, indicating that the patch delivery system could result in clinically effective drug concentrations in those areas of the cervical stroma where pre-cancerous lesions characteristic of cervical intraepithelial neoplasia can occur. (C) 1997 Elsevier Science B.V.

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McCarron P, Woolfson AD, McCafferty DF, Price JH, Sidhu H, Hickey GI. Cytotoxicity of 5-fluorouracil released from a bioadhesive patch into uterine cervical tissue. 1997;151(1):69-74.