Ma Min, Di Hong-Jie, Zhang Hui, Yao Jun-Hong, Dong Jie, Yan Guo-Jun, Qiao Hong-Zhi, Chen Jun
a Pharmaceutical Research Laboratory, School of Pharmacy , Nanjing University of Chinese Medicine , Nanjing , PR China.
b Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine , Nanjing , PR China.
Drug Dev Ind Pharm. 2017 Dec;43(12):2055-2063. doi: 10.1080/03639045.2017.1371730. Epub 2017 Sep 15.
The phospholipid vesicle-based permeation assay (PVPA) model has recently been introduced as an in vitro model which can mimic stratum corneum (SC) barriers to estimate the skin permeability of drugs. The aim of this study was to evaluate whether the PVPA model was suitable for the evaluation of penetration enhancing effect of skin penetration enhancers (PE).
The PVPA model was optimized by changing the lipid composition of both small liposomes (SL), and large liposomes (LL). The barrier properties of the PVPA model were monitored by electrical resistance and permeability measurement of the fluorescent marker Rhodamine B (RB). Then the permeation studies of the five active compounds with different physicochemical properties, namely, ferulic acid, paeoniflorin, albiflorin, tetrahydrocolumbamine, and tetrahydropalmatine, were performed directly on PVPA model to evaluate the penetration enhancing effect of menthol.
The enhancement ratio (ER) ranking of the five active compounds observed using the optimized PVPA model was in accordance with what observed with Franz diffusion cell device using porcine ear skin. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis of PVPA model and porcine ear skin after treatment with menthol has shown similar mechanism of menthol which perturbs the SC lipid arrangement and extracts the SC lipids.
In summary, the optimized PVPA model was used for the first time for the evaluation of the permeation enhancing effect. The optimized PVPA model has shown potential to be applied in a more standardized, cheaper, and ethical way for the screening of PE.
基于磷脂囊泡的渗透测定（PVPA）模型最近被引入作为一种体外模型，它可以模拟角质层（SC）屏障来估计药物的皮肤渗透性。本研究的目的是评估PVPA模型是否适用于评估皮肤渗透促进剂（PE）的促渗效果。
通过改变小脂质体（SL）和大脂质体（LL）的脂质组成来优化PVPA模型。通过对荧光标记物罗丹明B（RB）的电阻和渗透率测量来监测PVPA模型的屏障特性。然后直接在PVPA模型上对五种具有不同理化性质的活性化合物，即阿魏酸、芍药苷、白花芍药苷、四氢小檗胺和延胡索乙素进行渗透研究，以评估薄荷醇的促渗效果。
使用优化后的PVPA模型观察到的五种活性化合物的增强比（ER）排名与使用猪耳皮肤的Franz扩散池装置观察到的结果一致。用薄荷醇处理后对PVPA模型和猪耳皮肤进行衰减全反射-傅里叶变换红外光谱（ATR-FTIR）分析，结果表明薄荷醇的作用机制相似，即扰乱SC脂质排列并提取SC脂质。
总之，优化后的PVPA模型首次用于评估促渗效果。优化后的PVPA模型已显示出有潜力以更标准化、更便宜且符合伦理的方式应用于PE的筛选。
