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...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.展开更多
基金This work was supported in part by the University of Texas at Austin,College of Pharmacy and a grant from the National Institutes of Health(CA135274)to Z.CuiYoussef Naguib was supported by a doctoral scholarship from the Egyptian Ministry of Higher EducationThe authors acknowledge Cynergy,LLC(Carson City,NV)for generously providing Dermaroller s micro-needle rollers,free of charge.
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(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.
