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

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(500μm in length,50μm 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.