Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Division of Biomolecular and Cellular Medicine, Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden.
Clin Transl Med. 2024 Aug;14(8):e70002. doi: 10.1002/ctm2.70002.
Pharmacokinetics (PK) and pharmacodynamics (PD) are central concepts to guide the dosage and administration of drug therapies and are essential to consider for both healthcare professionals and researchers in therapeutic planning and drug discovery. PK/PD properties of a drug significantly influence variability in response to treatment, including therapeutic failure or excessive medication-related harm. Furthermore, suboptimal PK properties constitute a significant barrier to further development for some candidate treatments in drug discovery. This article describes how extracellular vesicles (EVs) affect different aspects of PK and PD of medications and their potential to modulate PK and PD properties to address problematic PK/PD profiles of drugs. We reviewed EVs' intrinsic effects on cell behaviours and medication responses. We also described how surface and cargo modifications can enhance EV functionalities and enable them as adjuvants to optimise the PK/PD profile of conventional medications. Furthermore, we demonstrated that various bioengineering strategies can be used to modify the properties of EVs, hence enhancing their potential to modulate PK and PD profile of medications.
This review uncovers the critical role of EVs in PK and PD modulation and motivates further research and the development of assays to unfold EVs' full potential in solving PK and PD-related problems. However, while we have shown that EVs play a vital role in modulating PK and PD properties of medications, we postulated that it is essential to define the context of use when designing and utilising EVs in pharmaceutical and medical applications.
Existing solutions for pharmacokinetics and pharmacodynamics modulation are limited. Extracellular vesicles can optimise pharmacokinetics as a drug delivery vehicle. Biogenesis and administration of extracellular vesicles can signal cell response. The pharmaceutical potential of extracellular vesicles can be enhanced by surface and cargo bioengineering. When using extracellular vesicles as modulators of pharmacokinetics and pharmacodynamics, the 'context of use' must be considered.
药代动力学（PK）和药效动力学（PD）是指导药物治疗剂量和给药的核心概念，对于治疗计划和药物发现中的医疗保健专业人员和研究人员都是必不可少的。药物的 PK/PD 特性显著影响治疗反应的可变性，包括治疗失败或过度的药物相关伤害。此外，对于药物发现中的一些候选治疗方法，PK 特性不理想是进一步开发的重大障碍。本文描述了细胞外囊泡（EVs）如何影响药物的 PK 和 PD 的不同方面，以及它们调节 PK 和 PD 特性以解决药物 PK/PD 特征不理想的潜在能力。我们综述了 EVs 对细胞行为和药物反应的内在影响。我们还描述了如何通过表面和货物修饰来增强 EV 的功能，并将其用作辅助剂来优化常规药物的 PK/PD 特征。此外，我们证明了各种生物工程策略可用于修饰 EV 的特性，从而增强其调节药物 PK 和 PD 特征的潜力。
本综述揭示了 EVs 在 PK 和 PD 调节中的关键作用，并促使进一步研究和开发测定法以充分发挥 EV 在解决 PK 和 PD 相关问题方面的潜力。然而，尽管我们已经表明 EVs 在调节药物的 PK 和 PD 特性方面发挥了至关重要的作用，但我们假设在设计和利用 EV 在药物和医疗应用中时，定义其使用背景至关重要。
现有的 PK 和 PD 调节解决方案有限。细胞外囊泡可用作药物递送载体来优化药代动力学。细胞外囊泡的生物发生和给药可信号传递细胞反应。通过表面和货物生物工程可增强细胞外囊泡的药物潜力。当将细胞外囊泡用作 PK 和 PD 调节剂时，必须考虑“使用背景”。
