University of Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier 73 B1.73.12, 1200 Brussels, Belgium.
Adv Drug Deliv Rev. 2021 Aug;175:113795. doi: 10.1016/j.addr.2021.05.005. Epub 2021 May 12.
Oral administration is the most commonly used route for drug delivery owing to its cost-effectiveness, ease of administration, and high patient compliance. However, the absorption of orally delivered compounds is a complex process that greatly depends on the interplay between the characteristics of the drug/formulation and the gastrointestinal tract. In this contribution, we review the different preclinical models (in vitro, ex vivo and in vivo) from their development to application for studying the transport of drugs across intestinal barriers. This review also discusses the advantages and disadvantages of each model. Furthermore, the authors have reviewed the selection and validation of these models and how the limitations of the models can be addressed in future investigations. The correlation and predictability of the intestinal transport data from the preclinical models and human data are also explored. With the increasing popularity and prevalence of orally delivered drugs/formulations, sophisticated preclinical models with higher predictive capacity for absorption of oral formulations used in clinical studies will be needed.
口服给药因其成本效益高、给药方便和患者顺应性好而成为最常用的药物递送途径。然而，口服给予的化合物的吸收是一个复杂的过程，很大程度上取决于药物/制剂的特性和胃肠道之间的相互作用。在本贡献中，我们回顾了不同的临床前模型（体外、离体和体内），从其开发到应用，以研究药物穿过肠道屏障的转运。本综述还讨论了每种模型的优缺点。此外，作者还回顾了这些模型的选择和验证，以及如何在未来的研究中解决模型的局限性。还探讨了临床前模型和人体数据中肠转运数据的相关性和可预测性。随着口服给予的药物/制剂越来越受欢迎和普遍，在临床研究中使用的口服制剂的吸收具有更高预测能力的复杂临床前模型将是必要的。
