Butnarasu Cosmin, Garbero Olga Valentina, Petrini Paola, Visai Livia, Visentin Sonja
Department of Molecular Biotechnology and Health Science, University of Turin, via Quarello 15, 10135 Torino, Italy.
Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, 20133 Milan, Italy.
Pharmaceutics. 2023 Jan 22;15(2):380. doi: 10.3390/pharmaceutics15020380.
Permeability across cellular membranes is a key factor that influences absorption and distribution. Before absorption, many drugs must pass through the mucus barrier that covers all the wet surfaces of the human body. Cell-free in vitro tools currently used to evaluate permeability fail to effectively model the complexity of mucosal barriers. Here, we present an in vitro mucosal platform as a possible strategy for assessing permeability in a high-throughput setup. The PermeaPad 96-well plate was used as a permeability system and further coupled to a pathological, tridimensional mucus model. The physicochemical determinants predicting passive diffusion were determined by combining experimental and computational approaches. Drug solubility, size, and shape were found to be the critical properties governing permeability, while the charge of the drug was found to be influential on the interaction with mucus. Overall, the proposed mucosal platform could be a promising in vitro tool to model the complexity of mucosal tissues and could therefore be adopted for drug-permeability profiling.
跨细胞膜的通透性是影响吸收和分布的关键因素。在吸收之前，许多药物必须穿过覆盖人体所有湿润表面的黏液屏障。目前用于评估通透性的无细胞体外工具无法有效模拟黏膜屏障的复杂性。在此，我们提出一种体外黏膜平台，作为在高通量设置中评估通透性的一种可能策略。PermeaPad 96孔板用作通透性系统，并进一步与病理性三维黏液模型相结合。通过结合实验和计算方法确定了预测被动扩散的物理化学决定因素。发现药物的溶解度、大小和形状是控制通透性的关键特性，而药物的电荷被发现对与黏液的相互作用有影响。总体而言，所提出的黏膜平台可能是一种很有前景的体外工具，可用于模拟黏膜组织的复杂性，因此可用于药物通透性分析。
