Gładysz Magdalena Z, Stevanoska Maja, Włodarczyk-Biegun Małgorzata K, Nagelkerke Anika
Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, P.O. Box 196, XB20, 9700 AD Groningen, the Netherlands; Polymer Science, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG, the Netherlands.
Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, P.O. Box 196, XB20, 9700 AD Groningen, the Netherlands.
Adv Drug Deliv Rev. 2022 May;184:114183. doi: 10.1016/j.addr.2022.114183. Epub 2022 Mar 9.
Pharmaceutical compounds are the main pillar in the treatment of various illnesses. To administer these drugs in the therapeutic setting, multiple routes of administration have been defined, including ingestion, inhalation, and injection. After administration, drugs need to find their way to the intended target for high effectiveness, and this penetration is greatly dependent on obstacles the drugs encounter along their path. Key hurdles include the physical barriers that are present within the body and knowledge of those is indispensable for progress in the development of drugs with increased therapeutic efficacy. In this review, we examine several important physical barriers, such as the blood-brain barrier, the gut-mucosal barrier, and the extracellular matrix barrier, and evaluate their influence on drug transport and efficacy. We explore various in vitro model systems that aid in understanding how parameters within the barrier model affect drug transfer and therapeutic effect. We conclude that physical barriers in the body restrict the quantity of drugs that can pass through, mainly as a consequence of the barrier architecture. In addition, the specific physical properties of the tissue can trigger intracellular changes, altering cell behavior in response to drugs. Though the barriers negatively influence drug distribution, physical stimulation of the surrounding environment may also be exploited as a mechanism to control drug release. This drug delivery approach is explored in this review as a potential alternative to the conventional ways of delivering therapeutics.
药物化合物是治疗各种疾病的主要支柱。为了在治疗环境中施用这些药物，已经定义了多种给药途径，包括口服、吸入和注射。给药后，药物需要找到通往预期靶点的途径以实现高效，而这种渗透在很大程度上取决于药物在其路径中遇到的障碍。关键障碍包括体内存在的物理屏障，了解这些屏障对于开发具有更高治疗效果的药物至关重要。在本综述中，我们研究了几种重要的物理屏障，如血脑屏障、肠道黏膜屏障和细胞外基质屏障，并评估它们对药物转运和疗效的影响。我们探索了各种体外模型系统，以帮助理解屏障模型中的参数如何影响药物传递和治疗效果。我们得出结论，体内的物理屏障限制了能够通过的药物数量，这主要是由于屏障结构所致。此外，组织的特定物理性质可引发细胞内变化，改变细胞对药物的反应行为。尽管这些屏障对药物分布有负面影响，但周围环境的物理刺激也可被用作控制药物释放的一种机制。本综述探讨了这种药物递送方法作为传统治疗药物递送方式的潜在替代方案。
