Department of Rheumatology of the First Hospital and Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
Department of Rheumatology of the First Hospital and Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China; College of Biology, Hunan University, Changsha, Hunan 410082, China.
J Control Release. 2022 Aug;348:42-56. doi: 10.1016/j.jconrel.2022.05.016. Epub 2022 Jun 2.
Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant of Sinomenium acutum (Thunb.) Rehd.et Wils. Currently, sinomenine hydrochloride (SIN) preparations, classified as a natural disease-modifying anti-rheumatic drug (nDMARD), have been used for therapy of rheumatoid arthritis (RA); however, the efficacy of SIN was seriously limited by its short half-life, low bioavailability, and dose-dependent adverse reactions. In this study, a biomimetic nanocomplex based on Prussian blue nanoparticles (PB NPs) was developed for overcoming clinical limitations of SIN and accordingly improving its efficacy. In vitro studies showed that the nanocomplexes significantly inhibited abnormal proliferation of fibroblast-like synoviocytes (FLSs) by scavenging reactive oxygen species (ROS) and inhibiting secretion of proinflammatory cytokines. In vivo imaging demonstrated that the improved immune-escape properties of the nanocomplexes resulted in markedly increased half-life of circulation and levels of accumulated drugs at arthritic sites of adjuvant-induced arthritis (AIA) rats. Notably, the nanocomplexes significantly suppressed joint inflammation and protected against bone destruction of AIA rats by inhibiting inflammatory cytokine secretion of the synovial macrophages and FLSs. These results indicate that the nanocomplexes provide an excellent carrier for controlled release and targeted accumulation of SIN within the arthritic sites, which consequently achieve disease-remitting effects of SIN on RA.
青藤碱是从中国药用植物青风藤（Thunb.）中分离得到的一种生物活性生物碱。目前，盐酸青藤碱（SIN）制剂被归类为天然疾病修饰抗风湿药物（nDMARD），已用于治疗类风湿关节炎（RA）；然而，SIN 的疗效受到半衰期短、生物利用度低和剂量依赖性不良反应的严重限制。在这项研究中，开发了一种基于普鲁士蓝纳米粒子（PB NPs）的仿生纳米复合物，以克服 SIN 的临床限制，从而提高其疗效。体外研究表明，纳米复合物通过清除活性氧（ROS）和抑制促炎细胞因子的分泌，显著抑制成纤维样滑膜细胞（FLS）的异常增殖。体内成像表明，纳米复合物的免疫逃逸特性得到改善，导致循环半衰期和关节炎部位累积药物水平显著增加，佐剂诱导关节炎（AIA）大鼠。值得注意的是，纳米复合物通过抑制滑膜巨噬细胞和 FLS 中炎症细胞因子的分泌，显著抑制关节炎大鼠的关节炎症和骨破坏。这些结果表明，纳米复合物为 SIN 在关节炎部位的控制释放和靶向积累提供了一种极好的载体，从而实现了 SIN 对 RA 的疾病缓解作用。
