Arthritis of joints remains a hard-to-treat disease due to the low drug exposure to the articular cavity. Present study was intended to develop a Tripterine (TRI) and all-trans retinoic acid (ATRA)-loaded lipid-polymer hybrid nanoparticles (ATLP) for enhanced antiarthritic efficacy in arthritis conditions. We have showed that two drugs could be loaded with high loading capacity and control the release kinetics in a pH-responsive manner. The ATLP showed strong inhibitory effects on the expressions of TNF-α, IL-6 and IL-1β in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at the in vitro conditions. Compared to individual drugs (TRI and ATRA), ATLP significantly reduced the paw thickness exhibiting potent inhibition of inflammation. Consistently, ATLP resulted in lowest clinical score compared to that of individual drug indicating the remarkable improvement in the recession of inflammation. We have clearly demonstrated that the nanoparticulate based co-delivery of drugs could abolish the adverse effects of free drug as indicated by the body weight changes. Importantly, ATLP resulted in significant reduction of mRNA of TNF-α, IL-6, IFN-ϒ and IL-17 compared to either free drugs or CIA mice. Overall, ATLP represent a promising therapeutic strategy for the treatment of arthritis conditions.

中文翻译：

---

雷公藤红素和全反式视黄酸（ATRA）负载脂质聚合物混合纳米颗粒，用于对抗炎性关节炎的协同抗关节炎治疗。


由于关节腔的药物暴露量低，关节关节炎仍然是一种难以治疗的疾病。本研究旨在开发一种负载雷公藤红素 (TRI) 和全反式视黄酸 (ATRA) 的脂质聚合物混合纳米粒子 (ATLP)，以增强关节炎疾病的抗关节炎功效。我们已经证明两种药物可以具有高负载能力并以 pH 响应方式控制释放动力学。在体外条件下，ATLP对脂多糖（LPS）刺激的RAW264.7细胞中TNF-α、IL-6和IL-1β的表达显示出强烈的抑制作用。与单独的药物（TRI 和 ATRA）相比，ATLP 显着降低了爪子厚度，表现出有效的炎症抑制作用。一致的是，与单独药物相比，ATLP 的临床评分最低，表明炎症消退有显着改善。我们已经清楚地证明，基于纳米颗粒的药物共同递送可以消除游离药物的副作用，如体重变化所示。重要的是，与游离药物或 CIA 小鼠相比，ATLP 导致 TNF-α、IL-6、IFN-ϒ 和 IL-17 的 mRNA 显着减少。总体而言，ATLP 代表了治疗关节炎疾病的一种有前途的治疗策略。