Recent advances in cell-based in vitro models for predicting drug permeability across brain, intestinal, and pulmonary barriers.

Bassma Eltanameli, Janny Piñeiro-Llanes, Rodrigo Cristofoletti
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Abstract

Introduction: Recent years have witnessed remarkable progress in the development of cell-based in vitro models aimed at predicting drug permeability, particularly focusing on replicating the barrier properties of the blood-brain barrier (BBB), intestinal epithelium, and lung epithelium.

Area covered: This review provides an overview of 2D in vitro platforms, including monocultures and co-culture systems, highlighting their respective advantages and limitations. Additionally, it discusses tools and techniques utilized to overcome these limitations, paving the way for more accurate predictions of drug permeability. Furthermore, this review delves into emerging technologies, particularly microphysiological systems (MPS), encompassing static platforms such as organoids and dynamic platforms like microfluidic devices. Literature searches were performed using PubMed and Google Scholar. We focus on key terms such as in vitro permeability models, MPS, organoids, intestine, BBB, and lungs.

Expert opinion: The potential of these MPS to mimic physiological conditions more closely offers promising avenues for drug permeability assessment. However, transitioning these advanced models from bench to industry requires rigorous validation against regulatory standards. Thus, there is a pressing need to validate MPS to industry and regulatory agency standards to exploit their potential in drug permeability prediction fully. This review underscores the importance of such validation processes to facilitate the translation of these innovative technologies into routine pharmaceutical practice.

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基于细胞的体外模型在预测药物跨脑、肠和肺屏障渗透性方面的最新进展。
引言:近年来,旨在预测药物渗透性的基于细胞的体外模型的开发取得了显著进展,尤其是在复制血脑屏障(BBB)、肠上皮细胞和肺上皮细胞的屏障特性方面:本综述概述了二维体外平台,包括单培养基和共培养系统,重点介绍了它们各自的优势和局限性。此外,它还讨论了克服这些局限性的工具和技术,为更准确地预测药物渗透性铺平了道路。此外,本综述还深入探讨了新兴技术,尤其是微生理系统(MPS),包括有机体等静态平台和微流体设备等动态平台。我们使用 PubMed 和 Google Scholar 进行了文献检索。我们重点关注体外渗透性模型、MPS、有机体、肠道、BBB 和肺等关键术语:这些 MPS 有可能更接近地模拟生理条件,为药物渗透性评估提供了前景广阔的途径。然而,要将这些先进的模型从实验室应用到工业领域,需要根据监管标准进行严格的验证。因此,迫切需要根据行业和监管机构的标准对 MPS 进行验证,以充分挖掘其在药物渗透性预测方面的潜力。本综述强调了此类验证过程对促进这些创新技术转化为常规制药实践的重要性。
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