Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø the Arctic University of Norway, Universitetsveien 57, Tromsø, 9037, Norway.
Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø the Arctic University of Norway, Universitetsveien 57, Tromsø, 9037, Norway; Pharmaceutical Design and Drug Delivery, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
Int J Pharm. 2018 Feb 15;537(1-2):213-222. doi: 10.1016/j.ijpharm.2017.12.038. Epub 2017 Dec 26.
The mucus layer covering all mucosal surfaces in our body is the first barrier encountered by drugs before their potential absorption through epithelial tissues, and could thus affect the drugs' permeability and their effectiveness. Therefore, it is of key importance to have in vitro permeability models that can mimic this specific environment. For this purpose, the novel mucus phospholipid vesicle-based permeation assay (mucus-PVPA) has been developed and used for permeability screening of drugs and formulations. The model proved to be stable under the chosen conditions and demonstrated the ability to discriminate between compounds with different chemical structures and properties. Overall, a decrease in drug permeability was found in the presence of mucus on top of the PVPA barriers, as expected. Moreover, mucoadhesive (chitosan-coated) and mucopenetrating (PEGylated) liposomes were investigated in the newly developed model. The mucus-PVPA was able to distinguish between the different liposomal formulations, confirming the penetration potential of the tested formulations and the related drug permeability. The mucus-PVPA model appears to be a promising in vitro tool able to mimic the environment of mucosal tissues, and could therefore be used for further drug permeability screening and formulation development.
覆盖我们身体所有黏膜表面的黏液层是药物在通过上皮组织被潜在吸收之前遇到的第一道屏障，因此可能会影响药物的通透性及其效果。因此，建立能够模拟这种特定环境的体外渗透性模型至关重要。为此，开发了新型基于黏液磷脂囊泡的渗透测定法（mucus-PVPA），并用于药物和制剂的渗透性筛选。该模型在所选条件下表现稳定，并证明了区分具有不同化学结构和性质的化合物的能力。总体而言，正如预期的那样，在 PVPA 屏障上存在黏液时，药物的渗透性会降低。此外，在新开发的模型中研究了具有黏膜黏附性（壳聚糖包被）和黏膜穿透性（PEG 化）的脂质体。黏液-PVPA 能够区分不同的脂质体配方，证实了测试配方的穿透潜力及其相关药物的渗透性。黏液-PVPA 模型似乎是一种有前途的体外工具，能够模拟黏膜组织的环境，因此可用于进一步的药物渗透性筛选和制剂开发。
