title: The effect of microneedles on the skin permeability and antitumor activity of topical 5-fluorouracil.
abstract: Topical 5-fluorouracil (5-FU) is approved for the treatment of superficial basal cell carcinoma and actinic keratosis. However, 5-FU suffers from poor skin permeation. Microneedles have been successfully applied to improve the skin permeability of small and large molecules, and even nanoparticles, by creating micron-sized pores in the stratum corneum layer of the skin. In this report, the feasibility of using microneedles to increase the skin permeability of 5-FU was tested. Using full thickness mouse skin mounted on Franz diffusion apparatus, it was shown that the flux of 5-FU through the skin was increased by up to 4.5-fold when the skin was pretreated with microneedles (500 µm in length, 50 µm in base diameter). In a mouse model with B16-F10 mouse melanoma cells implanted in the subcutaneous space, the antitumor activity of a commercially available 5-FU topical cream (5%) was significantly enhanced when the cream was applied on a skin area that was pretreated with microneedles, as compared to when the cream was simply applied on a skin area, underneath which the tumor cells were implanted, and without pretreatment of the skin with microneedles. Fluorouracil is not approved for melanoma therapy, but the clinical efficacy of topical 5-FU against tumors such as basal cell carcinoma may be improved by integrating microneedle technology into the therapy.
authors.affiliation: The University of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX 78712.
authors.forename: Youssef W
authors.initials: YW
authors.lastname: Naguib
authors.affiliation: The University of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX 78712.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: The University of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX 78712.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
keywords: Cytotoxicity; antitumor activity; flux; immunohistochemistry; melanoma; transdermal