Menthol towards 5-FU

Borneol and menthol were two terpenes wildly used as penetrate enhancer in 14 transdermal drug delivery. To explore their penetration enhancement effect towards hydrophilic 15 drug, 5-FU was selected as model drug. A method combined vitro permeation studies and coarse 16 grain molecular dynamics was used to investigate their penetration enhancement effect towards 17 5-FU. As a result, although both borneol and menthol showed a penetration enhancement effect 18 towards 5-FU, they differed a lot in the penetration enhancement mechanism, which was also 19 thought to account for their different penetration enhancement effect. As for menthol, SC bilayer 20 disrupting effect seemed to be its main mechanism. While for borneol, its mechanism seemed to be 21 more complicated. Except for disrupting the SC bilayer, it could also increase the permeation of 22 5-FU by enhancing the diffusion rate of 5-FU or inducing the formation of transient pore. All of this 23 enable us a molecular understanding of borneol and menthol’s penetration enhancement effect 24 towards hydrophilic drug, which might provide some guidance in the latter research and 25 application. 26