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J Invest Dermatol. 2007 May;127(5):1205-9. Epub 2007 Jan 11.

Imaging the prodrug-to-drug transformation of a 5-fluorouracil derivative in skin by confocal Raman microscopy.

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  • 1Department of Chemistry, Newark College of Arts and Sciences, Rutgers University, Newark, New Jersey 07102, USA.


The widespread adoption of transdermal drug delivery has been limited by the barrier properties of the outermost layer of the epidermis, the stratum corneum (SC). A variety of approaches have been developed to overcome the barrier, including the use of a prodrug form of an active therapeutic agent to enhance transdermal delivery. Once in the epidermis, the pro-molecule is converted to the active drug by endogenous enzymes or simple chemical hydrolysis. The prodrug selected for the current studies, 1-ethyloxycarbonyl-5-fluorouracil, is known to enhance transdermal delivery of 5-fluorouracil, an important systemic antitumor drug. Using confocal Raman microscopy on pigskin biopsies treated with prodrug, we are able to image the spatial distribution of both prodrug and drug in the SC and viable epidermis, thereby providing information about permeation and metabolism. This approach may readily be extended to a variety of dermatological processes.

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