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基于小干扰RNA的脑出血治疗:药物递送系统的挑战与进展

Small interfering RNAs based therapies for intracerebral hemorrhage: challenges and progress in drug delivery systems.

作者信息

Almarghalani Daniyah A, Boddu Sai H S, Ali Mohammad, Kondaka Akhila, Ta Devin, Shah Rayyan A, Shah Zahoor A

机构信息

Department of Pharmacology and Experimental Therapeutics; Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates.

出版信息

Neural Regen Res. 2022 Aug;17(8):1717-1725. doi: 10.4103/1673-5374.332129.

Abstract

Intracerebral hemorrhage (ICH) is a subtype of stroke associated with higher rates of mortality. Currently, no effective drug treatment is available for ICH. The molecular pathways following ICH are complicated and diverse. Nucleic acid therapeutics such as gene knockdown by small interfering RNAs (siRNAs) have been developed in recent years to modulate ICH's destructive pathways and mitigate its outcomes. However, siRNAs delivery to the central nervous system is challenging and faces many roadblocks. Existing barriers to systemic delivery of siRNA limit the use of naked siRNA; therefore, siRNA-vectors developed to protect and deliver these therapies into the specific-target areas of the brain, or cell types seem quite promising. Efficient delivery of siRNA via nanoparticles emerged as a viable and effective alternative therapeutic tool for central nervous system-related diseases. This review discusses the obstacles to siRNA delivery, including the advantages and disadvantages of viral and nonviral vectors. Additionally, we provide a comprehensive overview of recent progress in nanotherapeutics areas, primarily focusing on the delivery system of siRNA for ICH treatment.

摘要

脑出血(ICH)是一种与较高死亡率相关的中风亚型。目前,尚无针对脑出血的有效药物治疗方法。脑出血后的分子途径复杂多样。近年来,诸如通过小干扰RNA(siRNAs)进行基因敲低等核酸疗法已被开发出来,以调节脑出血的破坏途径并减轻其后果。然而,将siRNAs递送至中枢神经系统具有挑战性,且面临许多障碍。siRNA全身递送的现有障碍限制了裸siRNA的使用;因此,开发用于保护并将这些疗法递送至脑的特定靶区域或细胞类型的siRNA载体似乎很有前景。通过纳米颗粒有效递送siRNA成为用于中枢神经系统相关疾病的一种可行且有效的替代治疗工具。本综述讨论了siRNA递送的障碍,包括病毒载体和非病毒载体的优缺点。此外,我们全面概述了纳米治疗领域的最新进展,主要侧重于用于脑出血治疗的siRNA递送系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ccd/8820693/e68df44914a0/NRR-17-1717-g001.jpg

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