Silva Soraia, Bicker Joana, Falcão Amílcar, Fortuna Ana
Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; CIBIT - Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal.
Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; CIBIT - Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal.
Eur J Pharm Biopharm. 2023 Mar;184:62-82. doi: 10.1016/j.ejpb.2023.01.013. Epub 2023 Jan 22.
The intranasal route has been receiving greater attention from the scientific community not only for systemic drug delivery but also for the treatment of pulmonary and neurological diseases. Along with it, drug transport and permeability studies across the nasal mucosa have exponentially increased. Nevertheless, the translation of data from in vitro cell lines to in vivo studies is not always reliable, due to the difficulty in generating an in vitro model that resembles respiratory human physiology. Among all currently available methodologies, the air-liquid interface (ALI) method is advantageous to promote cell differentiation and optimize the morphological and histological characteristics of airway epithelium cells. Cells grown under ALI conditions, in alternative to submerged conditions, appear to provide relevant input for inhalation and pulmonary toxicology and complement in vivo experiments. Different methodologies and a variety of materials have been used to induce ALI conditions in primary cells and numerous cell lines. Until this day, with only exploratory results, no consensus has been reached regarding the validation of the ALI method, hampering data comparison. The present review describes the most adequate cell models of airway epithelium and how these models are differently affected by ALI conditions. It includes the evaluation of cellular features before and after ALI, and the application of the method in primary cell cultures, commercial 3D primary cells, cell lines and stem-cell derived models. A variety of these models have been recently applied for pharmacological studies against severe acute respiratory syndrome-coronavirus(-2) SARS-CoV(-2), namely primary cultures with alveolar type II epithelium cells and organotypic 3D models. The herein compiled data suggest that ALI conditions must be optimized bearing in mind the type of cells (nasal, bronchial, alveolar), their origin and the objective of the study.
鼻内给药途径不仅在全身药物递送方面，而且在肺部和神经疾病的治疗方面都受到了科学界越来越多的关注。与此同时，跨鼻黏膜的药物转运和通透性研究呈指数级增长。然而，由于难以建立一个类似于人类呼吸生理的体外模型，从体外细胞系到体内研究的数据转化并不总是可靠的。在所有目前可用的方法中，气液界面（ALI）方法有利于促进细胞分化，并优化气道上皮细胞的形态和组织学特征。与浸没条件相比，在ALI条件下生长的细胞似乎为吸入和肺部毒理学提供了相关数据，并补充了体内实验。不同的方法和多种材料已被用于在原代细胞和众多细胞系中诱导ALI条件。直到今天，由于只有探索性结果，关于ALI方法的验证尚未达成共识，这阻碍了数据比较。本综述描述了最适合的气道上皮细胞模型，以及这些模型如何受到ALI条件的不同影响。它包括对ALI前后细胞特征的评估，以及该方法在原代细胞培养、商业3D原代细胞、细胞系和干细胞衍生模型中的应用。最近，多种此类模型已被应用于针对严重急性呼吸综合征冠状病毒（-2）（SARS-CoV（-2））的药理学研究，即肺泡II型上皮细胞原代培养和器官型3D模型。本文汇编的数据表明，必须根据细胞类型（鼻、支气管、肺泡）、其来源和研究目的来优化ALI条件。
