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

• Published in: Acta pharmaceutica Sinica. B 2014-02, Vol.4 (1), p.94-99
• Main Authors: Naguib, Youssef W, Kumar, Amit, Cui, Zhengrong
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Antitumor activity; Cytotoxicity; Flux; Immunohistochemistry; Melanoma; Microneedles; Original; Skin permeability; Transdermal
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2013.12.013

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.