INSERM, U1059, Dysfonction Vasculaire et Hémostase, Saint-Etienne, France; Université de Lyon, Saint-Etienne F-42023, France.
Université de Lyon, Saint-Etienne F-42023, France; Laboratoire de biologie, d'ingénierie et d'imagerie de la greffe de cornée, BiiGC, EA2521 Saint-Etienne, France.
Eur J Pharm Biopharm. 2019 Jun;139:186-196. doi: 10.1016/j.ejpb.2019.04.002. Epub 2019 Apr 3.
The preclinical evaluation of nasally administered drug candidates requires screening studies based on in vitro models of the nasal mucosa. The aim of this study was to evaluate the morpho-functional characteristics of the 3D MucilAir™ nasal model with a pharmacological focus on [ATP]-binding cassette (ABC) efflux transporters. We initially performed a phenotypic characterization of the MucilAir™ model and assessed its barrier properties by immunofluorescence (IF), protein mass spectrometry and examination of histological sections. We then focused on the functional expression of the ABC transporters P-glycoprotein (P-gp), multidrug resistance associated protein (MRP)1, MRP2 and breast cancer resistance protein (BCRP) in bidirectional transport experiments. The MucilAir™ model comprises a tight, polarized, pseudo-stratified nasal epithelium composed of fully differentiated ciliated, goblet and basal cells. These ABC transporters were all expressed by the cell membranes. P-gp and BCRP were both functional and capable of actively effluxing substrates. The MucilAir™ model could consequently represent a potent tool for evaluating the interaction of nasally administered drugs with ABC transporters.
鼻腔给药候选药物的临床前评估需要基于鼻腔黏膜的体外模型进行筛选研究。本研究旨在评估 3D MucilAir™ 鼻腔模型的形态-功能特征，重点关注 [ATP]-结合盒（ABC）外排转运体。我们首先对 MucilAir™ 模型进行了表型特征描述，并通过免疫荧光（IF）、蛋白质质谱分析和组织学切片检查评估了其屏障特性。然后，我们专注于 ABC 转运体 P 糖蛋白（P-gp）、多药耐药相关蛋白（MRP）1、MRP2 和乳腺癌耐药蛋白（BCRP）在双向转运实验中的功能表达。MucilAir™ 模型由紧密、极化、假分层的鼻腔上皮组成，包含完全分化的纤毛细胞、杯状细胞和基底细胞。这些 ABC 转运体均表达在细胞膜上。P-gp 和 BCRP 均具有功能，能够主动外排底物。因此，MucilAir™ 模型可以成为评估鼻腔给药药物与 ABC 转运体相互作用的有力工具。
