冰片对氟尿嘧啶经皮促透作用的多尺度研究

Multi-scale study of borneol on the transdermal effect of fluorouracil

目的研究冰片对氟尿嘧啶的经皮促透作用,探究冰片对亲水性药物的促透机理。方法采用体外透皮实验、透射电子显微镜和介观分子动力学模拟等方法,分别对氟尿嘧啶的自身渗透性和冰片对其的促透作用进行多尺度研究。结果氟尿嘧啶难以穿透角质层,最大渗透速率(0.82μg/cm^2)和单位面积累计渗透量(20.45μg/cm^2)均较低,在冰片的促透作用下,氟尿嘧啶的渗透速率和渗透量均增大,当冰片浓度为1%时,氟尿嘧啶的渗透速率[13.58μg/(cm^2·h)]和24小时单位面积累计渗透量(325.50μg/cm^2)较高,促渗比达16.57倍,且对角质层结构影响不大,为冰片促透氟尿嘧啶的最佳浓度;冰片的促透作用主要表现为疏松角质层中脂质的排列,促进其中水通道的形成,从而促进氟尿嘧啶透过。结论冰片可以促进亲水性氟尿嘧啶经皮渗透,其主要促透机理为疏松角质层脂质排列,促进水通道的形成。

Objective To investigate the penetration enhancement mechanism of borneolto on fluorouracil,and to explore the permeation mechanism of borneol on hydrophilic drugs.Methods The in vitro permeation experiments,transmission electron microscopic and microscopic molecular dynamics model was used to study the penetration of fluorouracil and the permeation enhancement of borneol.Results Fluorouracil was difficult to penetrate the stratum corneum,the maximum penetration rate was 0.82 μg/（cm2·h）, and cumulative osmolality after 24h （20.45 μg/cm2） was low;with the enhancement effect of borneol, both penetration rate and cumulative osmolality of fluorouracil was increased, when the concentration of borneol was 1%, penetration rate[13.58 μg/（cm2·h）] and cumulative osmolality after 24h（325.50 μg/cm2） were the maximum value, the enhancement ratio was 16.57, and it had little effect on the stratum corneum structure, so 1% was the optimum concentration;Borneol can make the membrane lipid become loose and can promote the formation of water channels, thereby promoting the hydrophilic drugs penetration across.Conclusion Borneol can effectively promote the permeation of hydrophilic fluorouracil, the mechanism may be loosing the stratum corneum lipids and promoting the formation of water channels.