氨基酸酯类离子液体的经皮促渗活性考察

Investigation of Skin Permeation Enhancement of Amino Acid Ester Ionic Liquids

考察了氨基酸酯离子液体的体外经皮促渗活性,并评价其皮肤刺激性。以13种氨基酸酯离子液体为促渗剂,小鼠皮肤为药物模型,采用Franz扩散池法考察离子液体对模型药物睾酮的促渗作用;采用经皮水分散失速率仪,测定离子液体对皮肤通透性的影响;以荧光素钠为探针,采用荧光共聚焦显微镜,研究离子液体的皮肤促渗强度和促渗深度;最后以大鼠为模型动物,对离子液体的皮肤刺激性进行考察。结果表明,氨基酸离子液体能提高药物的溶解度,并改善皮肤的通透性,从而对睾酮产生促渗作用,促渗比最高可达10.96。经皮水分散失速率和荧光共聚焦显微镜考察结果表明,离子液体能够增强皮肤通透性,如小鼠皮肤经5%[SerC_1]Cl处理1 h,可使荧光渗透深度达到皮下500mm。皮肤刺激性试验中未观察到氨基酸酯离子液体对大鼠皮肤有刺激性,提示其安全性较高。

The promotion activity of skin permeability and skin irritation of amino acid ester ionic liquids（[AAE]X） were investigated. Franz diffusion cell experiments were employed to measure the permeation enhancements of 13 kinds of [AAE]X on testosterone through the excised mouse skin. Transepidermal water loss （TEWL） was used to evaluate the influence of [AAE]X on skin permeability. Confocal laser scanning microscopy （CLSM） examination was performed to evaluate the permeation intensity and depth of fluorescein sodium. Skin irritation test of [AAE]Xs was carried out with SD rats as model animals. The results showed that [AAE]Xs could improve the solubility of the drug and increase the skin permeability, resulting in the permeation enhancement of the model drug with the highest enhance ratio of 10.96. The results of TEWL and CLSM showed that ionic liquids also could moderate the skin barrier properties so as to ehance the permeation intensity and depth. The depth in mouse skin reached 500 μm after treated with 5% [SerC1]Cl for 1 h. No significant changes were observed druing skin irritation test with SD rats as animal models, indicating [AAE]Xs were rather safety.