化学促渗剂与负极性驻极体促进5-氟尿嘧啶体外透过大鼠增生性瘢痕和背部皮肤的比较

目的 比较化学促渗剂和负极性驻极体对5-氟尿嘧啶（5-FU）体外经增生性瘢痕皮肤的促渗作用，为驻极体5-FU缓控释贴剂的制备奠定基础。方法 通过Franz扩散池和高效液相色谱仪，研究1%氮酮、10%油酸乙酯、-1 000 V驻极体、-1 500 V驻极体和-2 000 V驻极体作用后5-FU的体外经大鼠瘢痕皮肤或背部皮肤的透皮规律。结果 （1）1%氮酮和10%油酸乙酯均可促进5-FU经大鼠瘢痕皮肤的渗透，且10%油酸乙酯的促渗效果优于1%氮酮。（2）化学促渗剂作用下的5-FU经大鼠瘢痕皮肤和背部皮肤的体外渗透规律相似，但是5-FU经瘢痕皮肤的累积透皮量少于经背部皮肤的累积透皮量。（3）负极性驻极体对5-FU均具有良好的促渗作用，促渗效果的优劣顺序依次为：-2 000 V驻极体、-1 500 V驻极体、-1 000 V驻极体。同样，负极性驻极体作用下5-FU经大鼠瘢痕皮肤的累积透过量少于经背部皮肤的累积透皮量。结论 化学促渗剂和负极性驻极体均能促进5-FU的经皮渗透。其中，10%油酸乙酯和-2 000 V驻极体对5-FU的促渗效果最佳，可用于驻极体5-FU缓控释贴剂的制备。

Chemical penetration enhancers and negative electret in promoting in vitro percutaneous penetration of 5-fluorouracil through rat scar and dorsal skin: a comparative study

Objective To compare the effects of chemical penetration enhancers and negative electret in promoting percutaneous penetration of 5-fluorouracil (5-FU) through rat scar and dorsal skin in vitro, so as to lay a foundation for preparing delayed-release 5-FU electret transdermal patch. Methods The in vitro transdermal behaviors of 5-FU through rat scar and dorsal skin under the actions of 1% azone, 10% ethyl oleate, -1 000 V electret, -1 500 V electret and -2 000 V electret were studied using improved Franze diffusion cell and high performance liquid chromatography (HPLC). Results (1) Both 1% azone and 10% ethyl oleate promoted the penetration of 5-FU through rat scar and dorsal skin, with the promoting effect of 10% ethyl oleate being better than that of 1% azone. (2) Although the transdermal behaviors of 5-FU were similar through scar skin and dorsal skin at the presence of chemical enhancers, the cumulative penetration amount through the scar skin was less than that through the dorsal skin. (3) The negative electrets used in this study had satisfactory penetration promoting effect, with the promoting effect from strong to weak being -2 000 V electret > -1 500 V electret > -1 000 V electret. Moreover, the scar skin also had less cumulative penetration amount of 5-FU than that of the dorsal skin under the action of electrets. Conclusion Both the chemical enhancers and electrets can enhance the transdermal delivery of 5-FU. 10% ethyl oleate and -2 000 V electret have the best enhancing effect on 5-FU transdermal delivery and can be considered for preparation of 5-FU electret transdermal patch.