The effect of microneedles on the skin permeability and antitumor activity of topical 5-fluorouracil

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• 作者：Youssef W. Naguib^&dagger ; ; Amit Kumar^&dagger ; ; Zhengrong Cui ; ^{zhengrong.cui@austin.utexas.edu" class="auth_mail}
• 关键词：Microneedles ; 5-Fluorouracil ; Cytotoxicity ; Melanoma ; Immunohistochemistry ; Flux ; Transdermal ; Antitumor activity ; Skin permeability
• 刊名：Acta Pharmaceutica Sinica B
• 出版年：February, 2014
• 年：2014
• 卷：4
• 期：1
• 页码：94-99
• 全文大小：3907 K

文摘

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 渭m in length, 50 渭m 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.