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细胞外囊泡是否为神经疾病临床药物递送带来新希望?

Are extracellular vesicles new hope in clinical drug delivery for neurological disorders?

机构信息

Department of Biochemistry, Usmanu Danfodiyo University, Sokoto, Nigeria.

出版信息

Neurochem Int. 2021 Mar;144:104955. doi: 10.1016/j.neuint.2021.104955. Epub 2021 Jan 5.

DOI:10.1016/j.neuint.2021.104955
PMID:33412233
Abstract

Cells secrete extracellular vesicles (EVs) for intercellular communication. EVs are natural nanovesicles that are surrounded by lipid bilayer for delivery of assorted cargoes for therapeutic purposes. In addition to their therapeutic roles, these vesicles are potential drug delivery systems. Exosomes are the most studied EVs as the delivery carriers that can cross the blood-brain barrier (BBB) because of their nanosize. BBB is a diffusion barrier that is selective for small molecules to transit from blood to the brain. This barrier has been an obstacle for the delivery of drugs to the brain for the treatment of neurological disorders (NDs). For efficient drug delivery, synthetic vesicles such as liposomes have been employed as carriers for delivery of therapeutic molecules in clinical practice. However, these delivery systems are not without drawbacks. Among the limitations of these drug carriers include recognition by the body as foreign particles that encounter multiple defence systems that could recognize, neutralize and eliminate them. EVs are natural vesicles that may circumvent the body defence system to remain in systemic circulation for a long time. This unique property made them excellent drug delivery vehicles for clinical application. Here I discuss the progress, challenges and future directions of EVs (especially exosomes) as vehicles for targeted delivery of drug and at the same time deliver their cargoes for regenerative purposes in NDs. Recent developments in bioengineering and microfluidic technologies, which hold promise for clinical-grade production of EVs as drug delivery systems for NDs are also highlighted.

摘要

细胞通过分泌细胞外囊泡(EVs)进行细胞间通讯。EVs 是天然的纳米囊泡,由脂质双层包围,用于传递各种货物以达到治疗目的。除了治疗作用外,这些囊泡还是有潜力的药物递送系统。外泌体是研究最多的 EVs 作为递药载体,因为它们的纳米尺寸可以跨越血脑屏障(BBB)。BBB 是一种对小分子具有选择性的扩散屏障,使其能够从血液中转运到大脑。由于这个屏障的存在,药物很难递送到大脑中,从而难以治疗神经疾病(NDs)。为了实现有效的药物递送,合成囊泡如脂质体已被用作载体,用于在临床实践中递送治疗分子。然而,这些递送系统并非没有缺点。这些药物载体的局限性之一包括被身体识别为外来颗粒,从而遇到多种防御系统,这些系统可以识别、中和和消除它们。EVs 是天然囊泡,可能绕过身体防御系统,在全身循环中长时间存在。这种独特的特性使它们成为临床应用中优秀的药物递送载体。在这里,我讨论了 EVs(特别是外泌体)作为靶向递药载体的进展、挑战和未来方向,同时也讨论了它们在 NDs 中的再生目的下递药的能力。还强调了生物工程和微流控技术的最新进展,这些技术有望实现 EVs 作为 NDs 药物递送系统的临床级生产。

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