PDF(Pubmed)
Abstract：
Rheumatoid arthritis (RA) is a chronic autoimmune disease of yet undetermined etiology that is accompanied by significant oxidative stress, inflammatory responses, and damage to joint tissues. In this study, we designed chondroitin sulfate (CS)-modified tragacanth gum-gelatin composite nanocapsules (CS-Cur-TGNCs) loaded with curcumin nanocrystals (Cur-NCs), which rely on the ability of CS to target CD44 to accumulate drugs in inflamed joints. Cur was encapsulated in the form of nanocrystals into tragacanth gum-gelatin composite nanocapsules (TGNCs) by using an inborn microcrystallization method, which produced CS-Cur-TGNCs with a particle size of approximately 80 ± 11.54 nm and a drug loading capacity of 54.18 ± 5.17%. In an in vitro drug release assay, CS-Cur-TGNCs showed MMP-2-responsive properties. During the treatment of RA, CS-Cur-TGNCs significantly inhibited oxidative stress, promoted the polarization of M2-type macrophages to M1-type macrophages, and decreased the expression of inflammatory factors (TNF-α, IL-1β, and IL-6). In addition, it also exerted excellent anti-inflammatory effects, and significantly alleviated the swelling of joints during the treatment of gouty arthritis (GA). Therefore, CS-Cur-TGNCs, as a novel drug delivery system, could lead to new ideas for clinical therapeutic regimens for RA and GA.
摘要：
类风湿性关节炎（RA）是一种病因尚未确定的慢性自身免疫性疾病，伴有明显的氧化应激，炎症反应，和关节组织的损伤。在这项研究中,我们设计了负载姜黄素纳米晶体（Cur-NCs）的硫酸软骨素（CS）修饰的黄芪胶-明胶复合纳米胶囊（CS-Cur-TGNCs），这依赖于CS靶向CD44的能力在发炎的关节中积累药物。Cur以纳米晶体的形式封装到黄芪胶-明胶复合纳米胶囊（TGNCs）通过使用先天性微晶方法，其产生具有约80±11.54nm的粒径和54.18±5.17%的载药量的CS-Cur-TGNC。在体外药物释放试验中，CS-Cur-TGNC显示MMP-2反应特性。在RA的治疗过程中,CS-Cur-TGNCs显著抑制氧化应激,促进M2型巨噬细胞向M1型巨噬细胞的极化，并降低炎症因子(TNF-α,IL-1β,和IL-6）。此外,它还发挥了优异的抗炎作用，并显著缓解痛风性关节炎(GA)治疗过程中关节肿胀。因此,CS-Cur-TGNC,作为一种新型的药物递送系统，可以为RA和GA的临床治疗方案提供新的思路。
