Rheumatoid arthritis (RA) is a systemic autoimmune disease which could not only cause inflammatory reaction, but also cause cartilage and bone damage. The clinical treatment is mainly aimed at anti-inflammatory and immunotherapy. Targeting both at inflammation and bone damage repairing will be great significance for RA therapy. Triptolide has high efficiency of anti-inflammatory and anti-immune. And reported it had the effect of bone damage repairing on RA rats. But serious toxicity limits its development and application. In this study we prepared lipid cubic crystal nanoparticles gels of triptolide (TP-LCNPS-GEL) to treat rheumatoid arthritis by transdermal delivery. Temperature sensitivity and microstructure of TP-LCNPS-GEL was characterized. TP-LCNPS-GEL greatly improved percutaneous permeability, prolong biological half-life, average retention time and bioavailability of triptolide. The animal experiment results show that TP-LCNPS-GEL enhanced the effects on anti-inflammatory and bone protection of triptolide with low toxicity. All results indicated that TP-LCNPS-GEL as a transdermal delivery preparation is an excellent choice for rheumatoid arthritis.

类风湿关节炎（RA）是一种全身性自身免疫性疾病，不仅会引起炎症反应，还会引起软骨和骨损伤。临床治疗主要针对抗炎和免疫治疗。同时针对炎症和骨损伤修复对 RA 治疗具有重要意义。雷公藤内酯具有高效的抗炎和抗免疫作用。并报道其对RA大鼠具有骨损伤修复作用。但严重的毒性限制了它的开发和应用。在这项研究中，我们制备了雷公藤内酯类脂质立方晶体纳米颗粒凝胶（TP-LCNPS-GEL），通过透皮给药治疗类风湿性关节炎。表征了 TP-LCNPS-GEL 的温度敏感性和微观结构。TP-LCNPS-GEL 大大提高了经皮通透性，延长了生物半衰期，雷公藤内酯的平均保留时间和生物利用度。动物实验结果表明，TP-LCNPS-GEL增强了雷公藤甲素的抗炎和骨保护作用，且毒性低。所有结果表明，作为透皮给药制剂的 TP-LCNPS-GEL 是治疗类风湿性关节炎的绝佳选择。