(A) Normal skin architecture showing hair follicle and blood vessel organization; some perifollicular blood vessels have been outlined. (B) Topical application of Nile Red dye in an ethanol:water vehicle to the skin surface, followed 30 min later by frozen section and fluorescence microscopy of skin sections, shows that delivery of the small molecule dye into the skin occurs almost entirely via hair follicle channels. (C) (i) normal skin architecture with some perifollicular blood vessels outlined; (ii) hypothetical depiction of red dye diffusion, as an example for epinephrine diffusion, from the hair follicle base into surrounding tissue that contains perifollicular blood vessels; (iii) hypothetical depiction showing that systemically administered chemotherapy is retained within the lumen of the constricted, perifollicular blood vessels with little or no diffusion to the surrounding hair follicle stem cells; (iv) hypothetical depiction showing that systemically administered chemotherapy readily diffuses to surrounding structures, including hair follicle stem cells, from non-constricted perifollicular blood vessels.