Engesland André, Škalko-Basnet Nataša, Flaten Gøril Eide
Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø, The Arctic University of Norway, Tromsø, N-9037, Norway.
J Pharm Sci. 2015 Mar;104(3):1119-27. doi: 10.1002/jps.24315. Epub 2014 Dec 30.
Cost-effective and efficient methods for permeability screening are crucial during early development of drugs, drug formulations, and cosmeceuticals. Alternatives to animal experiments are impelled for both economical and ethical reasons. The aim of this study was to determine the ability of the phospholipid vesicle-based permeation assay (PVPA) to assess the effect of different formulations on drug permeability and thus establish its utility in formulation development. Three model drugs were tested in solutions and as liposomal formulations. The permeability results for the PVPA models were compared with the results for the reconstructed human skin model, EpiSkin(®). The drugs were ranked based on their estimated penetration potentials, and the results were in accordance with what was expected considering the physicochemical properties of the drugs. PVPAs (E-80, ceramide, cholesterol, cholesteryl sulfate, and palmitic acid) was able to distinguish between drug solutions and liposomal formulations; however, EpiSkin(®) detected only small differences between the drugs in solution and formulations. In contrast with EpiSkin(®), which is limited by a 3-day testing window, PVPA barriers can be stored frozen for up to 2 weeks or even up to 16 months, depending on their compositions. The PVPA models are thus more cost effective and efficient than the EpiSkin(®) model for permeability screening during early drug development.
在药物、药物制剂和药妆品的早期开发过程中，具有成本效益且高效的渗透性筛选方法至关重要。出于经济和伦理原因，人们迫切需要动物实验的替代方法。本研究的目的是确定基于磷脂囊泡的渗透测定法（PVPA）评估不同制剂对药物渗透性影响的能力，从而确定其在制剂开发中的实用性。对三种模型药物在溶液和脂质体制剂中的情况进行了测试。将PVPA模型的渗透性结果与重建的人体皮肤模型EpiSkin(®)的结果进行了比较。根据估计的渗透潜力对药物进行了排名，结果与考虑到药物理化性质所预期的情况一致。PVPA（E-80、神经酰胺、胆固醇、硫酸胆固醇和棕榈酸）能够区分药物溶液和脂质体制剂；然而，EpiSkin(®)仅检测到溶液和制剂中药物之间的微小差异。与受3天测试窗口限制的EpiSkin(®)不同，PVPA屏障可根据其成分冷冻保存长达2周甚至16个月。因此，在药物早期开发过程中的渗透性筛选方面，PVPA模型比EpiSkin(®)模型更具成本效益且效率更高。
