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用于增强类风湿性关节炎治疗的共递送羟氯喹和小干扰RNA的创新脂质纳米颗粒

Innovative Lipid Nanoparticles Co-Delivering Hydroxychloroquine and siRNA for Enhanced Rheumatoid Arthritis Therapy.

作者信息

Feng Yanru, Pan Xintong, Li Ziqian, Li Yue, Sun Ya'nan, Yang Shaokun, He Chaoxing, Dang Yunjie, Huang Lu, Xiang Bai

机构信息

Department of Pharmaceutics, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, China.

Hebei Key Laboratory of Innovative Drug Research and Evaluation, Hebei Medical University, Shijiazhuang 050017, China.

出版信息

Pharmaceutics. 2025 Jan 1;17(1):45. doi: 10.3390/pharmaceutics17010045.

DOI:10.3390/pharmaceutics17010045
PMID:39861693
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11769357/
Abstract

Rheumatoid arthritis (RA) is a debilitating autoimmune disorder characterized by chronic inflammation and joint damage. Despite advancements in treatment, complete remission remains elusive. In this study, we introduce a novel lipid nanoparticle formulation co-delivering hydroxychloroquine (HCQ) and siRNA targeting TNF-α (si) using microfluidic technology, marking the first use of such a combination for RA therapy. In LPS-stimulated RAW 264.7 cells, the nanoparticles effectively reduced inflammatory markers. When administered via an intra-articular injection in a rat model, they significantly decreased joint inflammation and demonstrated good biological safety. This pioneering approach highlights the potential of lipid nanoparticles as a dual-delivery platform for enhanced RA treatment through targeted intra-articular administration.

摘要

类风湿性关节炎(RA)是一种使人衰弱的自身免疫性疾病,其特征为慢性炎症和关节损伤。尽管治疗取得了进展,但完全缓解仍难以实现。在本研究中,我们使用微流控技术引入了一种新型脂质纳米颗粒制剂,该制剂可共同递送羟氯喹(HCQ)和靶向TNF-α的小干扰RNA(si),这是首次将这种组合用于RA治疗。在脂多糖刺激的RAW 264.7细胞中,纳米颗粒有效降低了炎症标志物。当通过关节内注射给药于大鼠模型时,它们显著减轻了关节炎症并显示出良好的生物安全性。这种开创性方法突出了脂质纳米颗粒作为双重递送平台,通过靶向关节内给药增强RA治疗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc86/11769357/1021d357c327/pharmaceutics-17-00045-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc86/11769357/8259a21e67a5/pharmaceutics-17-00045-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc86/11769357/3bf046d99ffb/pharmaceutics-17-00045-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc86/11769357/a5c0bac3e9b1/pharmaceutics-17-00045-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc86/11769357/8cc38536ffa5/pharmaceutics-17-00045-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc86/11769357/1021d357c327/pharmaceutics-17-00045-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc86/11769357/8259a21e67a5/pharmaceutics-17-00045-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc86/11769357/3bf046d99ffb/pharmaceutics-17-00045-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc86/11769357/a5c0bac3e9b1/pharmaceutics-17-00045-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc86/11769357/8cc38536ffa5/pharmaceutics-17-00045-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc86/11769357/1021d357c327/pharmaceutics-17-00045-g005.jpg

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本文引用的文献

1
Lipid nanoparticle-based strategies for extrahepatic delivery of nucleic acid therapies - challenges and opportunities.基于脂质纳米颗粒的非肝脏递药策略 - 挑战与机遇。
J Control Release. 2024 Jun;370:763-772. doi: 10.1016/j.jconrel.2024.04.022. Epub 2024 May 17.
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Proinflammatory phenotype of B10 and B10pro cells elicited by TNF-α in rheumatoid arthritis.TNF-α 在类风湿关节炎中诱导 B10 和 B10pro 细胞产生促炎表型。
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The landscape of nanoparticle-based siRNA delivery and therapeutic development.
基于纳米颗粒的小干扰RNA递送与治疗发展概况。
Mol Ther. 2024 Feb 7;32(2):284-312. doi: 10.1016/j.ymthe.2024.01.005. Epub 2024 Jan 10.
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Nanoparticle technology for mRNA: Delivery strategy, clinical application and developmental landscape.mRNA 纳米颗粒技术:递呈策略、临床应用和发展前景。
Theranostics. 2024 Jan 1;14(2):738-760. doi: 10.7150/thno.84291. eCollection 2024.
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Hydroxychloroquine as an important immunomodulator: a novel insight into an old drug.羟氯喹作为一种重要的免疫调节剂:老药新用的新视角。
Pol Arch Intern Med. 2024 Jan 29;134(1). doi: 10.20452/pamw.16656. Epub 2024 Jan 2.
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The presumable effects of hydroxychloroquine and its metabolites in the treatment of systemic lupus erythematosus.羟氯喹及其代谢物治疗红斑狼疮的推测作用。
Int Immunopharmacol. 2024 Jan 5;126:111269. doi: 10.1016/j.intimp.2023.111269. Epub 2023 Nov 25.
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The emerging potential of siRNA nanotherapeutics in treatment of arthritis.小干扰RNA纳米疗法在关节炎治疗中的新兴潜力。
Asian J Pharm Sci. 2023 Sep;18(5):100845. doi: 10.1016/j.ajps.2023.100845. Epub 2023 Sep 16.
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-Acetylcysteine overcomes epalrestat-mediated increase of toxic 4-hydroxy-2-nonenal and potentiates the anti-arthritic effect of epalrestat in AIA model.乙酰半胱氨酸克服依帕司他介导的毒性 4-羟基-2-壬烯醛增加,并增强依帕司他在 AIA 模型中的抗关节炎作用。
Int J Biol Sci. 2023 Aug 6;19(13):4082-4102. doi: 10.7150/ijbs.85028. eCollection 2023.
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Rheumatoid arthritis molecular targets and their importance to flavonoid-based therapy.类风湿性关节炎的分子靶点及其对基于黄酮类化合物治疗的重要性。
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Lipid Nanoparticles Optimized for Targeting and Release of Nucleic Acid.靶向和释放核酸的脂质纳米粒子的优化。
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