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新型透明质酸/姜黄素纳米胶束的抗炎和关节润滑双重作用提高类风湿关节炎治疗效果。

Anti-Inflammation and Joint Lubrication Dual Effects of a Novel Hyaluronic Acid/Curcumin Nanomicelle Improve the Efficacy of Rheumatoid Arthritis Therapy.

出版信息

ACS Appl Mater Interfaces. 2018 Jul 18;10(28):23595-23604. doi: 10.1021/acsami.8b06236. Epub 2018 Jul 2.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which can cause endless suffering to the patients and severely impact their normal lives. To treat RA, the drugs in use have many serious side effects, high cost, or only focus on their anti-inflammatory mechanisms without taking joint lubrication into consideration. Therefore, in this study, we aim to construct a novel anti-RA drug composed of hyaluronic acid/curcumin (HA/Cur) nanomicelle to resolve these problems. Characterizations show that Cur is bound to HA by ester linkages and self-assembles to form a spherical nanomicelle with a diameter of around 164 nm under the main driving of the hydrophilic and hydrophobic forces. The nanomicelle enjoys excellent biocompatibility that effectively promotes the proliferation of chondrocytes. When injected to the RA rats, the nanomicelle significantly lowers the edema degree of the arthritic rats compared to other groups; more critically, a dramatic decrease in friction between the surfaces of cartilage around the joints has been found, which protects the cartilage from the RA-induced damage. Additionally, systematic mechanism investigation indicates that the nanomicelle diminishes the expression of related cytokines and vascular endothelial growth factor, finally leading to the excellent performance. The newfound nanomicelle has a potential for clinical practice of RA therapy, which will contribute significantly to alleviating the pain of patients and improving the quality of life for them.

摘要

类风湿关节炎(RA)是一种慢性炎症性自身免疫性疾病,会给患者带来无尽的痛苦,并严重影响他们的正常生活。为了治疗 RA,目前使用的药物有许多严重的副作用、成本高,或者只关注其抗炎机制,而不考虑关节润滑。因此,在这项研究中,我们旨在构建一种由透明质酸/姜黄素(HA/Cur)纳米胶束组成的新型抗 RA 药物,以解决这些问题。特性研究表明,Cur 通过酯键与 HA 结合,并在亲水性和疏水性的主要驱动下自组装成直径约 164nm 的球形纳米胶束。纳米胶束具有优异的生物相容性,能有效促进软骨细胞的增殖。当将纳米胶束注射到 RA 大鼠中时,与其他组相比,纳米胶束能显著降低关节炎大鼠的肿胀程度;更重要的是,发现在关节周围软骨的表面之间的摩擦有明显减少,这可以保护软骨免受 RA 引起的损伤。此外,系统的机制研究表明,纳米胶束降低了相关细胞因子和血管内皮生长因子的表达,最终表现出优异的性能。这种新发现的纳米胶束具有 RA 治疗的临床应用潜力,将极大地减轻患者的痛苦,提高他们的生活质量。

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