丙酸氯倍他索脂肪酸囊泡的经皮渗透性及抗银屑病药效的初步研究

Preliminary study on the transcutaneous permeability and anti-psoriasis effect of clobetasolpropioate fatty acid vesicles

目的 考察丙酸氯倍他索脂肪酸囊泡(CP-FAV)的体外渗透性及对银屑病模型小鼠的疗效。方法 通过Franz扩散池进行体外透皮研究,差示扫描热分析方法(DSC)和傅里叶变换红外光谱(FTIR)考察脂肪酸囊泡对皮肤结构的影响。构建小鼠银屑病模型,以银屑病皮损面积及严重程度指数(PASI)评估小鼠皮损情况;以苏木素-伊红(HE)染色病理分析皮损组织形态学变化。结果 CP-FAV能够有效提高CP的透皮吸收能力,其体外渗透曲线拟合后符合一级动力学方程,可有效持续地进行透皮释放;脂肪酸囊泡可以改变脂质的有序性,提高角质层的类脂质流动性,促进丙酸氯倍他索在皮肤角质层的渗透转移。与模型组比较,CP-FAV组可以显著降低PASI评分(P<0.05),改善银屑病样小鼠皮损情况;HE染色表明小鼠皮损组织表皮层厚度均显著减小,真皮层炎性细胞浸润程度均显著减轻。结论 脂肪酸囊泡可增加CP在皮肤局部应用的渗透能力,降低皮肤对药物的屏障,达到抗银屑病的作用,是一种新型的治疗银屑病的局部给药系统。

Objective To investigate the in vitro permeability of clobetasolpropioatefatty acid vesicles(CP-FAV)and its efficacy in psoriasis model mice.Methods The in vitro transdermal study was conducted by Franz diffusion pool,and the effect of fatty acid vesicles on skin structure was investigated by differential scanning thermal analysis(DSC)and Fourier transform infrared spectroscopy(FTIR).Mouse psoriasis model was constructed to evaluate skin lesions by psoriasis area and severity index(PASI),and hematoxylin-eosin(HE)staining was used to analyze the histopathological changes of the lesions.Results The in vitro transdermal assay showed that CP-FAV could effectively improve the transdermal absorption capacity of CP,and its diffusion curve in vitro fitted the first-order kinetic equation,which could effectively and continuously release CP through skin.FTIR results showed that fatty acid vesicles could change lipid ordering,and DSC results showed that fatty acid vesicles could improve cuticle lipid mobility and promote the osmotic transfer of clobetasol propionate in skin cuticle.The results of pharmacodynamic experiments showed that the CP-FAV group could significantly reduce PASI score(P<0.05)and improve the skin damage of psoriasis-like mice compared with the model group;HE staining showed that the thickness of the epidermal layer in mouse skin lesions and the inflammatory cell infiltration in the dermis of mice were significantly reduced.Conclusion Fatty acid vesicles could increase the permeability of CP for local application in the skin,and reduce the skin barrier to drugs.It is a new local delivery system for the treatment of psoriasis.