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用于高效研究药物被动渗透性的新型仿生屏障Permeapad™。

New biomimetic barrier Permeapad™ for efficient investigation of passive permeability of drugs.

作者信息

di Cagno Massimiliano, Bibi Hanady A, Bauer-Brandl Annette

机构信息

Drug Transport and Delivery Research Group, Department of Pharmacy, Arctic University of Norway, Tromsø, Norway.

Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark.

出版信息

Eur J Pharm Sci. 2015 Jun 20;73:29-34. doi: 10.1016/j.ejps.2015.03.019. Epub 2015 Mar 31.

Abstract

In this work the suitability of a newly invented physical patch comprising a biomimetic barrier (named Permeapad™) for drug permeability tests has been investigated. Exemplars of Permeapad™ were adapted to Franz diffusion cells and apparent permeability (Papp) of a series of drugs were measured and compared with calculated partition coefficients (logPcal) of the investigated drugs as well as literature reference values obtained from Parallel Artificial Membrane Permeation Assay (PAMPA) and the cellular based method Caco-2. Moreover, tightness of the barrier to hydrophilic marker's permeation, resistance of these barriers to proton permeation (pH changes) and shelf-life functionality were also investigated. Comparison with the published data indicated a good correlation between the permeability values measured and partition coefficients (logPcal). Moreover, a good correlation between the permeabilities measured with the new barrier and well-established in vitro permeability methods (PAMPA and Caco-2 respectively) was found for both highly absorbed and poorly permeable compounds. Permeapad™ also proved to maintain high integrity over time and in different pH environments. In conclusion, Permeapad™ as an innovative barrier appears to be a promising tool for fast, cost effective and reliable screening of drugs and chemical entities' passive permeability.

摘要

在本研究中,对一种新发明的包含仿生屏障(名为Permeapad™)的物理贴片用于药物渗透性测试的适用性进行了研究。将Permeapad™样本适配于Franz扩散池,测量了一系列药物的表观渗透率(Papp),并与所研究药物的计算分配系数(logPcal)以及从平行人工膜渗透试验(PAMPA)和基于细胞的Caco-2方法获得的文献参考值进行了比较。此外,还研究了屏障对亲水性标记物渗透的紧密性、这些屏障对质子渗透(pH变化)的抗性以及保质期功能。与已发表数据的比较表明,所测量的渗透率值与分配系数(logPcal)之间具有良好的相关性。此外,对于高吸收性和低渗透性化合物,在新屏障上测得的渗透率与成熟的体外渗透方法(分别为PAMPA和Caco-2)之间均发现了良好的相关性。Permeapad™还被证明能在不同时间和不同pH环境下保持高完整性。总之,Permeapad™作为一种创新屏障,似乎是快速、经济高效且可靠地筛选药物和化学实体被动渗透性的一种有前景的工具。

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