基于经皮微透析的桉油在体促渗活性及其皮肤刺激性评价

目的考察桉油作为经皮促渗剂的皮肤刺激性与在体经皮促渗活性,为其在外用制剂中的合理应用提供数据支持。方法采用CCK-8实验测定桉油对人永生化表皮细胞(HaCaT细胞)的细胞毒性,利用皮肤水分流失(TEWL)仪测定桉油对大鼠腹皮完整性的影响,评价其作为经皮促渗剂的皮肤刺激性;选择川芎嗪和栀子苷为亲脂性和亲水性模型药物,利用反向渗析法测定微透析探针对模型药物的在体回收率,测定在桉油作用下对川芎嗪和栀子苷的皮肤药动学行力的影响。结果桉油对HaCaT细胞的半数抑制浓度(IC50)为2.452 mmol/L,显著高于常用化学促渗剂氮酮的0.266 mmol/L,同时桉油作用下对大鼠皮肤TEWL值具有一定影响,但弱于氮酮,提示桉油可能具有一定皮肤刺激性,但明显弱于氮酮;大鼠在体经皮微透析实验显示,桉油对川芎嗪和栀子苷的经皮促渗倍数(ER)分别为11.40和13.79,提示其对亲脂性和亲水性药物均具良好的在体促渗效果,对亲水性药物的促渗作用稍好,虽然桉油的整体促渗效果弱于氮酮,但对川芎嗪的促渗倍数与氮酮(ER=15.89)相接近。结论桉油对亲脂性药物和亲水性药物具有良好的在体经皮促渗效果,且与化学促渗剂相比,具有相对温和的皮肤刺激性,这为其在外用制剂中的应用提供了数据支持。

In vivo transdermal permeation-enhancement activity and skin irritation of eucalyptus oil by using microdialysis technique

Objective To evaluate the skin irritation of eucalyptus oil and its in vivo transdermal penetration enhancement properties by using the cutaneous microdialysis technique. Methods The CCK-8 assay was used to measure the toxicity of eucalyptus oil on HaCaT cells, and the TEWL values of the rat skin was determined to investigate the effect of eucalyptus oil on the skin integrity and irritation. Ligustrazine and geniposide were chosen as lipophilic and hydrophilic model drugs, respectively, and their microdialysis probe in vivo recoveries were determined using the retrodialysis method. After treatment with eucalyptus oil, the skin pharmacodynamics behaviors of two model drugs were investigated to evaluate its penetration-enhancement activity. Results The cytotoxicity test revealed there IC₅₀ value of eucalyptus oil to HaCaT cells was 2.452 mmol/L, which was significantly higher than that of chemical penetration enhancer Azone (IC₅₀, 0.266 mmol/L). Meanwhile, the eucalyptus oil had a certain impact on the rat skin TEWL values, but it was weaker than Azone, this implied that the eucalyptus oil had a mild skin irritation. The in vivo transdermal microdialysis tests revealed that the enhancement ratios (ER) of ligustrazine and geniposide were 11.40 and 13.79, respectively, indicating that eucalyptus oil could effectively facilitate the transdermal permeation of both of lipophilic and hydrophilic drugs. Although the penetration enhancement property was generally weaker than Azone, the ER value of eucalyptus oil was closely approximate to Azone. Conclusion The eucalyptus oil could promote the transdermal permeation of both lipophilic and hydrophilic drugs with mild skin irritation, which provided the data support for its application in topical preparation.