Engesland André, Škalko-Basnet Nataša, Flaten Gøril Eide
a Department of Pharmacy, Drug Transport and Delivery Research Group , University of Tromsø The Arctic University of Norway , Tromsø , N-9037 , Norway.
Drug Dev Ind Pharm. 2016 Nov;42(11):1742-51. doi: 10.3109/03639045.2016.1171334. Epub 2016 Apr 13.
The phospholipid vesicle-based permeation assay (PVPA) is a recently established in vitro stratum corneum model to estimate the permeability of intact and healthy skin. The aim here was to further evolve this model to mimic the stratum corneum in a compromised skin barrier by reducing the barrier functions in a controlled manner.
To mimic compromised skin barriers, PVPA barriers were prepared with explicitly defined reduced barrier function and compared with literature data from both human and animal skin with compromised barrier properties. Caffeine, diclofenac sodium, chloramphenicol and the hydrophilic marker calcein were tested to compare the PVPA models with established models.
The established PVPA models mimicking the stratum corneum in healthy skin showed good correlation with biological barriers by ranking drugs similar to those ranked by the pig ear skin model and were comparable to literature data on permeation through healthy human skin. The PVPA models provided reproducible and consistent results with a distinction between the barriers mimicking compromised and healthy skin. The trends in increasing drug permeation with an increasing degree of compromised barriers for the model drugs were similar to the literature data from other in vivo and in vitro models.
The PVPA models have the potential to provide permeation predictions when investigating drugs or cosmeceuticals intended for various compromised skin conditions and can thus possibly reduce the time and cost of testing as well as the use of animal testing in the early development of drug candidates, drugs and cosmeceuticals.
基于磷脂囊泡的渗透测定法（PVPA）是一种最近建立的体外角质层模型，用于评估完整健康皮肤的渗透性。此处的目的是进一步改进该模型，通过以可控方式降低屏障功能来模拟皮肤屏障受损时的角质层。
为了模拟受损的皮肤屏障，制备了具有明确降低的屏障功能的PVPA屏障，并与来自具有受损屏障特性的人和动物皮肤的文献数据进行比较。测试了咖啡因、双氯芬酸钠、氯霉素和亲水性标记物钙黄绿素，以将PVPA模型与已建立的模型进行比较。
已建立的模拟健康皮肤角质层的PVPA模型与生物屏障具有良好的相关性，对药物的排序与猪耳皮肤模型的排序相似，并且与通过健康人类皮肤渗透的文献数据相当。PVPA模型提供了可重复且一致的结果，能够区分模拟受损皮肤和健康皮肤的屏障。模型药物的药物渗透随着屏障受损程度的增加而增加的趋势与来自其他体内和体外模型的文献数据相似。
PVPA模型在研究针对各种受损皮肤状况的药物或药妆品时具有提供渗透预测的潜力，因此有可能减少测试时间和成本，以及在候选药物、药物和药妆品的早期开发中减少动物试验的使用。
