Soriano-Meseguer Sara, Fuguet Elisabet, Port Adriana, Rosés Martí
Departament de Química Analítica i Institut de Biomedicina, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain.
Serra Húnter Programme, Generalitat de Catalunya, 08002 Barcelona, Spain.
ADMET DMPK. 2020 Mar 4;8(1):16-28. doi: 10.5599/admet.761. eCollection 2020.
In recent years, the parallel artificial membrane permeability assay (PAMPA) has been extended for prediction of skin permeation by developing an artificial membrane which mimics the stratum corneum structure, skin-PAMPA. In the present work, the different parameters affecting skin-PAMPA permeability, such as incubation time and stirring, have been studied to establish ideal assay conditions to generate quality data for a screening of active pharmaceutical ingredients (API) in early stage drug discovery. Another important parameter is membrane retention, which shows dependence on lipophilicity when compounds are in their neutral form. Furthermore, the stability of the membrane has been investigated at different pH values, especially at basic pHs. Finally, a good correlation between human skin permeability and skin-PAMPA permeability, with a large dataset (n = 46), has been established. The optimized assay conditions were an incubation time of 4 hours with stirring in a pH below 8. With all these considerations the thickness of the aqueous boundary layer is decreased as much as possible and the membrane stability is guaranteed.
近年来，通过开发一种模拟角质层结构的人工膜——皮肤平行人工膜渗透试验（skin-PAMPA），平行人工膜渗透试验（PAMPA）已被扩展用于预测皮肤渗透性。在本研究中，研究了影响skin-PAMPA渗透性的不同参数，如孵育时间和搅拌，以建立理想的试验条件，为早期药物发现中活性药物成分（API）的筛选生成高质量数据。另一个重要参数是膜保留率，当化合物呈中性形式时，膜保留率显示出对亲脂性的依赖性。此外，还研究了膜在不同pH值下的稳定性，特别是在碱性pH值下。最后，利用一个大型数据集（n = 46）建立了人体皮肤渗透性与skin-PAMPA渗透性之间的良好相关性。优化的试验条件是在pH低于8的条件下搅拌孵育4小时。综合所有这些因素，水相边界层的厚度尽可能减小，同时保证了膜的稳定性。
