Centre of Excellence for Pharmaceutical Sciences (Pharmacen), North-West University, Potchefstroom, South Africa.
Biopharm Drug Dispos. 2023 Feb;44(1):94-112. doi: 10.1002/bdd.2348. Epub 2023 Feb 20.
The intranasal route of administration provides a noninvasive method to deliver drugs into the systemic circulation and/or directly into the brain. Direct nose-to-brain drug delivery offers the possibility to treat central nervous system diseases more effectively, as it can evade the blood-brain barrier. In vitro and ex vivo intranasal models provide a means to investigate physiological and pharmaceutical factors that could play a role in drug delivery across the nasal epithelium as well as to determine the mechanisms involved in drug absorption from the nose. The development and implementation of cost-effective pharmacokinetic models for intranasal drug delivery with good in vitro-in vivo correlation can accelerate pharmaceutical drug product development and improve economic and ecological aspects by reducing the time and costs spent on animal studies. Special considerations should be made with regard to the purpose of the in vitro/ex vivo study, namely, whether it is intended to predict systemic or brain delivery, source and site of tissue or cell sampling, viability window of selected model, and the experimental setup of diffusion chambers. The type of model implemented should suit the relevant needs and requirements of the project, researcher, and interlaboratory. This review aims to provide an overview of in vitro and ex vivo models that have been developed to study intranasal and direct nose-to-brain drug delivery.
鼻腔给药途径为将药物递送至全身循环和/或直接递送至脑部提供了一种非侵入性方法。直接鼻脑递药有可能更有效地治疗中枢神经系统疾病，因为它可以避开血脑屏障。鼻内给药的体外和离体模型提供了一种手段，可用于研究在鼻上皮递药过程中可能起作用的生理和药物因素，并确定从鼻腔吸收药物所涉及的机制。开发和实施具有良好体外-体内相关性的、经济有效的鼻腔给药药代动力学模型，可以通过减少动物研究的时间和成本，加速药物产品的开发，并改善经济和生态方面。应该特别考虑到体外/离体研究的目的，即其是否旨在预测全身或脑部递药、组织或细胞采样的来源和部位、所选模型的存活窗口，以及扩散室的实验设置。所实施的模型类型应适合项目、研究人员和实验室间的相关需求和要求。本文综述旨在概述为研究鼻腔和直接鼻脑递药而开发的体外和离体模型。
