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Extracellular Vesicles as Drug Delivery Vehicles to the Central Nervous System

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Abstract

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.

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Funding

This study was funded by NIH/NIDA R01 grant awarded to SVY.

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Correspondence to Sowmya V. Yelamanchili.

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The author FS declares no conflict of interest. The author SC declares no conflict of interest and the author SVY declare no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Shahjin, F., Chand, S. & Yelamanchili, S.V. Extracellular Vesicles as Drug Delivery Vehicles to the Central Nervous System. J Neuroimmune Pharmacol 15, 443–458 (2020). https://doi.org/10.1007/s11481-019-09875-w

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  • DOI: https://doi.org/10.1007/s11481-019-09875-w

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