研究动态
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绿原酸缀合的纳米胶束可减轻实验性关节炎的疾病严重程度。

A chlorogenic acid-conjugated nanomicelle attenuates disease severity in experimental arthritis.

发表日期:2024 May 24
作者: Akshay Vyawahare, Chandrashekhar Jori, Jattin Kumar, Kanika, Mohammad Fareed, Nemat Ali, Kaushik Parida, Rehan Khan
来源: ARTHRITIS RESEARCH & THERAPY

摘要:

类风湿性关节炎(RA)是一种全身性免疫疾病,以滑膜炎、骨损伤和软骨侵蚀为特征,导致社会经济负担增加和生活质量下降。尽管其原因尚不清楚,但对其病理生理学理解的进步促进了新的治疗方法。目前的治疗方法,包括缓解疾病的抗风湿药物 (DMARD) 和生物制剂,通常会导致疗效低下和不必要的副作用。为了解决这些药物的局限性,基于载体的药物递送系统(例如纳米胶束)已成为一种有前途的解决方案。在本研究中,利用 PLGA(聚乳酸-乙醇酸)作为骨架合成了纳米胶束;该骨架与以抑制炎症而闻名的绿原酸 (CGA) 结合,并结合了甲氨蝶呤 (MTX),这是一种用于 RA 治疗的模型药物。纳米胶束在尺寸、电荷、药物负载和药物释放行为方面进行了广泛的表征。在胶原诱导的关节炎模型中对 MTX-PLGA-b-CGA 纳米胶束的体内评估表明,关节肿胀、软骨侵蚀和疾病严重程度显着减轻。此外,组织学结果证实了软骨完整性和关键促炎标志物的表达减少,包括核因子κβ配体受体激活剂(RANKL)和肿瘤坏死因子(TNF-α)。基于 MTX-PLGA-b-CGA 纳米胶束的方法为管理 RA 的严重程度和进展提供了一种生物相容性且潜在有效的治疗策略,为 RA 治疗提供了一种充满希望的替代方案。
Rheumatoid arthritis (RA) is a systemic immune disorder marked by synovitis, bone damage, and cartilage erosion, leading to increased socio-economic burdens and reduced quality of life. Despite its unknown cause, advancements in understanding its pathophysiology have facilitated novel therapeutic approaches. Current treatments, including disease-modifying anti-rheumatic drugs (DMARDs) and biologics, often result in low efficacy and unnecessary side effects. To address the limitations of these drugs, carrier-based drug delivery systems, such as nanomicelles, have emerged as a promising solution. In this study, nanomicelles were synthesised utilizing PLGA (poly(lactic-co-glycolic acid)) as a backbone; this backbone is conjugated with chlorogenic acid (CGA), which is known for suppressing inflammation, and incorporates methotrexate (MTX), a model drug that is established for RA treatment. The nanomicelles were extensively characterized in terms of size, charge, drug loading, and drug-release behaviour. The in vivo assessment of MTX-PLGA-b-CGA nanomicelles in a collagen-induced arthritis model demonstrated a remarkable reduction in joint swelling, cartilage erosion, and disease severity. Furthermore, histological findings confirmed cartilage integrity and reduced expression of key pro-inflammatory markers, including receptor activator of nuclear factor kappa beta ligand (RANKL) and tumor necrosis factor (TNF-α). The approach based on the MTX-PLGA-b-CGA nanomicelles presents a biocompatible and potentially effective therapeutic strategy for management of the severity and progression of RA, providing a hopeful alternative for RA treatment.