Andrographolide (AG) has favorable anti-inflammatory and antioxidative capacity. However, it has low bioavailability due to high lipophilicity and can be easily cleared by the synovial fluid after intra-articular injection, leading to low therapeutic efficiency in osteoarthritis (OA). Herein, we designed a nano-sized pH-responsive drug delivery system (DDS) for OA treatment by using modified mesoporous silica nanoparticles (MSNs) with pH-responsive polyacrylic acid (PAA) for loading of AG to form AG@MSNs-PAA nanoplatform. The nanoparticles have uniform size (∼120 nm), high drug loading efficiency (22.38 ± 0.71%) and pH-responsive properties, beneficial to sustained release in OA environment. Compared with AG, AG@MSNs-PAA showed enhanced antiarthritic efficacy and chondro-protective capacity based on IL-1β-stimulated chondrocytes and anterior cruciate ligament transection-induced rat OA model, as demonstrated by lower expression of inflammatory factors and better prevention of proteoglycan loss. Therefore, the AG@MSNs-PAA nanoplatform may be developed as a promising OA-specific and on-demand DDS.

中文翻译：

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一种基于 pH 响应介孔二氧化硅纳米粒子的药物递送系统，可控制释放穿心莲内酯，用于 OA 治疗

穿心莲内酯 (AG) 具有良好的抗炎和抗氧化能力。然而，由于其高亲脂性，其生物利​​用度较低，并且关节内注射后很容易被滑液清除，导致骨关节炎（OA）的治疗效率较低。在此，我们设计了一种用于OA治疗的纳米级pH响应性药物递送系统（DDS），使用改性介孔二氧化硅纳米颗粒（MSNs）和pH响应性聚丙烯酸（PAA）负载AG形成AG@MSNs-PAA纳米平台。该纳米颗粒具有均匀的尺寸（∼120 nm）、高载药效率（22.38±0.71%）和pH响应特性，有利于在OA环境中持续释放。与 AG 相比，AG@MSNs-PAA 在 IL-1β 刺激的软骨细胞和前交叉韧带横断诱导的大鼠 OA 模型中表现出增强的抗关节炎功效和软骨保护能力，炎症因子的表达较低，蛋白多糖的预防也更好。损失。因此，AG@MSNs-PAA 纳米平台可能被开发为一种有前途的 OA 专用且按需的 DDS。