In vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast

Oukseub Lee1, David Ivancic1, Robert T Chatterton Jr2, Alfred W Rademaker3, Seema A Khan11Department of Surgery, 2Department of Obstetrics/Gynecology, 3Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USAPurpose: Oral tamoxifen, a triphenylethylene...

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Autores principales:	Lee O, Ivancic D, Chatterton RT Jr, Rademaker AW, Khan SA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1f08520899d540c69712e1939f3baaf4
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spelling	oai:doaj.org-article:1f08520899d540c69712e1939f3baaf42021-12-02T00:58:11ZIn vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast1179-1314https://doaj.org/article/1f08520899d540c69712e1939f3baaf42011-07-01T00:00:00Zhttp://www.dovepress.com/in-vitro-human-skin-permeation-of-endoxifen-potential-for-local-transd-a7874https://doaj.org/toc/1179-1314Oukseub Lee1, David Ivancic1, Robert T Chatterton Jr2, Alfred W Rademaker3, Seema A Khan11Department of Surgery, 2Department of Obstetrics/Gynecology, 3Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USAPurpose: Oral tamoxifen, a triphenylethylene (TPE), is useful for breast cancer prevention, but its adverse effects limit acceptance by women. Tamoxifen efficacy is related to its major metabolites 4-hydroxytamoxifen (4-OHT) and N-desmethyl-4-hydroxytamoxifen (endoxifen [ENX]). Transdermal delivery of these to the breast may avert the toxicity of oral tamoxifen while maintaining efficacy. We evaluated the relative efficiency of skin permeation of 4-OHT and ENX in vitro, and tested oleic acid (OA) as a permeation-enhancer.Methods: 4-OHT, ENX, and estradiol (E2) (0.2 mg/mL of 0.5 &micro;Ci 3H/mg) were dissolved in 60% ethanol-phosphate buffer, &plusmn;OA (0.1%&ndash;5%). Permeation through EpiDermTM (Matek Corp, Ashland, MA) and split-thickness human skin was calculated based on the amount of the agents recovered from the receiver fluid and skin using liquid scintillation counting over 24 hours.Results: In the EpiDerm model, the absorption of 4-OHT and ENX was 10%&ndash;11%; total penetration (TP) was 26%&ndash;29% at 24 hours and was decreased by OA. In normal human skin, the absorption of 4-OHT and ENX was 0.3%; TP was 2%&ndash;4% at 24 hours. The addition of 1% OA improved the permeation of ENX significantly more than that of 4-OHT (P &lt; 0.004); further titration of OA at 0.25%&ndash;0.5% further improved the permeation of ENX to a level similar to that of estradiol.Conclusion: The addition of OA to ENX results in a favorable rapid delivery equivalent to that of estradiol, a widely used transdermal hormone. The transdermal delivery of ENX to the breast should be further developed in preclinical and clinical studies.Keywords: endoxifen, breast cancer prevention, human skin, transdermal, oleic acidLee OIvancic DChatterton RT JrRademaker AWKhan SADove Medical PressarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol 2011, Iss default, Pp 61-70 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lee O Ivancic D Chatterton RT Jr Rademaker AW Khan SA In vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast
description	Oukseub Lee1, David Ivancic1, Robert T Chatterton Jr2, Alfred W Rademaker3, Seema A Khan11Department of Surgery, 2Department of Obstetrics/Gynecology, 3Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USAPurpose: Oral tamoxifen, a triphenylethylene (TPE), is useful for breast cancer prevention, but its adverse effects limit acceptance by women. Tamoxifen efficacy is related to its major metabolites 4-hydroxytamoxifen (4-OHT) and N-desmethyl-4-hydroxytamoxifen (endoxifen [ENX]). Transdermal delivery of these to the breast may avert the toxicity of oral tamoxifen while maintaining efficacy. We evaluated the relative efficiency of skin permeation of 4-OHT and ENX in vitro, and tested oleic acid (OA) as a permeation-enhancer.Methods: 4-OHT, ENX, and estradiol (E2) (0.2 mg/mL of 0.5 &micro;Ci 3H/mg) were dissolved in 60% ethanol-phosphate buffer, &plusmn;OA (0.1%&ndash;5%). Permeation through EpiDermTM (Matek Corp, Ashland, MA) and split-thickness human skin was calculated based on the amount of the agents recovered from the receiver fluid and skin using liquid scintillation counting over 24 hours.Results: In the EpiDerm model, the absorption of 4-OHT and ENX was 10%&ndash;11%; total penetration (TP) was 26%&ndash;29% at 24 hours and was decreased by OA. In normal human skin, the absorption of 4-OHT and ENX was 0.3%; TP was 2%&ndash;4% at 24 hours. The addition of 1% OA improved the permeation of ENX significantly more than that of 4-OHT (P &lt; 0.004); further titration of OA at 0.25%&ndash;0.5% further improved the permeation of ENX to a level similar to that of estradiol.Conclusion: The addition of OA to ENX results in a favorable rapid delivery equivalent to that of estradiol, a widely used transdermal hormone. The transdermal delivery of ENX to the breast should be further developed in preclinical and clinical studies.Keywords: endoxifen, breast cancer prevention, human skin, transdermal, oleic acid
format	article
author	Lee O Ivancic D Chatterton RT Jr Rademaker AW Khan SA
author_facet	Lee O Ivancic D Chatterton RT Jr Rademaker AW Khan SA
author_sort	Lee O
title	In vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast
title_short	In vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast
title_full	In vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast
title_fullStr	In vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast
title_full_unstemmed	In vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast
title_sort	in vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/1f08520899d540c69712e1939f3baaf4
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In vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast

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