Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE, 68198-5800, USA.
Effective drug delivery to the CNS to achieve the desired therapeutic response is a significant challenge in the field of drug delivery. In central nervous system (CNS), blood brain barrier (BBB) restricts the desired therapeutic responses due to inefficient targeting, release kinetics, and failure to reach therapeutic concentrations in the brain. Therefore, most potentially beneficial diagnostic and therapeutic agents are not able to reach to the brain upon systemic administration. Despite the existence of many invasive techniques to promote drug deliveries across BBB, novel strategies of drug delivery system which can cross BBB effectively are required, otherwise translation of novel neurotherapeutics from bench to bedside will be difficult to achieve. In this review, we briefly outline the existing and emerging strategies for CNS drug deliveries with a focus on potential and challenges of using extracellular vesicles (EVs) in CNS drug delivery system. EVs are emerging as a promising tool for therapeutic delivery owing to its favorable intrinsic features of biocompatibility, stability, stealth capacity, ability to overcome natural barriers and inherent homing capability. EVs are nanovesicles that allow cell-cell communication. The EVs-cargo reflects the physiological as well as the pathophysiological state of a cell. EVs are shown to play a role in human immunodeficiency virus (HIV) infection and dissemination, which contributes to acquired immune deficiency syndrome (AIDS). In the context of HIV-1 infection, this review also outlines the role of EVs in dissemination, challenges faced in EVs research in HIV-1 co-morbid conditions and potential of nanotechnologies, especially EVs in Neuro-AIDS.
EVs are used for the delivery of small molecule drugs, protein, and nucleic acid to the CNS as well as imaging molecules for in vivo tracking. For the purpose of delivery, EVs may or may not be subjected to membrane modification. The advantages of EVs, including its biocompatibility, low immunogenicity, and low toxicity profiles, can be exploited to potentially devise novel therapeutic delivery system for CNS drug targeting. This article outlines the challenges in potential EV-based therapeutic delivery.
中文翻译：
细胞外囊泡作为中枢神经系统的药物输送载体。
有效地将药物递送到 CNS 以实现所需的治疗反应是药物递送领域的重大挑战。在中枢神经系统 (CNS) 中，血脑屏障 (BBB) 由于靶向、释放动力学和无法在大脑中达到治疗浓度而限制了所需的治疗反应。因此，大多数潜在有益的诊断和治疗剂在全身给药时不能到达大脑。尽管存在许多促进跨 BBB 药物递送的侵入性技术，但仍需要能够有效穿过 BBB 的药物递送系统的新策略，否则将难以实现将新型神经疗法从工作台转移到床边。在这次审查中，我们简要概述了中枢神经系统药物递送的现有和新兴策略，重点是在中枢神经系统药物递送系统中使用细胞外囊泡 (EV) 的潜力和挑战。EVs 因其生物相容性、稳定性、隐身能力、克服自然障碍的能力和固有的归巢能力等有利的内在特征而成为一种有前途的治疗工具。EVs 是允许细胞间通讯的纳米囊泡。EVs-cargo 反映了细胞的生理和病理生理状态。EVs 被证明在人类免疫缺陷病毒 (HIV) 感染和传播中发挥作用，这有助于获得性免疫缺陷综合征 (AIDS)。在 HIV-1 感染的背景下，本综述还概述了 EV 在传播中的作用，
EV 用于将小分子药物、蛋白质和核酸输送到 CNS 以及用于体内跟踪的成像分子。出于交付目的，EV 可能会或可能不会进行膜修饰。EVs 的优势，包括其生物相容性、低免疫原性和低毒性特征，可用于设计用于 CNS 药物靶向的新型治疗递送系统。本文概述了潜在的基于 EV 的治疗递送的挑战。
EVs are used for the delivery of small molecule drugs, protein, and nucleic acid to the CNS as well as imaging molecules for in vivo tracking. For the purpose of delivery, EVs may or may not be subjected to membrane modification. The advantages of EVs, including its biocompatibility, low immunogenicity, and low toxicity profiles, can be exploited to potentially devise novel therapeutic delivery system for CNS drug targeting. This article outlines the challenges in potential EV-based therapeutic delivery.
EVs are used for the delivery of small molecule drugs, protein, and nucleic acid to the CNS as well as imaging molecules for in vivo tracking. For the purpose of delivery, EVs may or may not be subjected to membrane modification. The advantages of EVs, including its biocompatibility, low immunogenicity, and low toxicity profiles, can be exploited to potentially devise novel therapeutic delivery system for CNS drug targeting. This article outlines the challenges in potential EV-based therapeutic delivery.
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