Zhang Faxing, Li Lu, Zhang Xinyuan, Yang Hongyu, Fan Yingzhen, Zhang Jian, Fang Ting, Liu Yaming, Nie Zhihao, Wang Dongkai
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Pharmaceutics. 2024 Apr 1;16(4):480. doi: 10.3390/pharmaceutics16040480.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to deformities and disabilities in patients. Conventional treatment focuses on delaying progression; therefore, new treatments are necessary. The present study reported a novel ionic liquid transdermal platform for efficient RA treatment, and the underlying mechanism was elucidated using FTIR, H-NMR, Raman, XPS, and molecular simulations. The results showed that the reversibility of the semi-ionic hydrogen bonding facilitated high drug loading and enhanced drug permeability. Actarit's drug loading had an approximately 11.34-times increase. The in vitro permeability of actarit and ketoprofen was improved by 5.46 and 2.39 times, respectively. And they had the same significant effect in vivo. Furthermore, through the integration of network pharmacology, Western blotting (WB), and radiology analyses, the significant osteoprotective effects of SIHDD-PSA (semi-ionic H-bond double-drug pressure-sensitive adhesive transdermal patch) were revealed through the modulation of the JAK-STAT pathway. The SIHDD-PSA significantly reduced paw swelling and inflammation in the rat model, and stimulatory properties evaluation confirmed the safety of SIHDD-PSA. In conclusion, these findings provide a novel approach for the effective treatment of RA, and the semi-ionic hydrogen bonding strategy contributes a new theoretical basis for developing TDDS.
类风湿性关节炎（RA）是一种慢性自身免疫性疾病，可导致患者出现畸形和残疾。传统治疗侧重于延缓疾病进展；因此，需要新的治疗方法。本研究报道了一种用于高效治疗RA的新型离子液体透皮给药平台，并使用傅里叶变换红外光谱（FTIR）、氢核磁共振（H-NMR）、拉曼光谱、X射线光电子能谱（XPS）和分子模拟阐明了其潜在机制。结果表明，半离子氢键的可逆性有助于实现高载药量并增强药物渗透性。阿克他利的载药量增加了约11.34倍。阿克他利和酮洛芬的体外渗透率分别提高了5.46倍和2.39倍。它们在体内也有同样显著的效果。此外，通过整合网络药理学、蛋白质免疫印迹法（WB）和放射学分析，揭示了半离子氢键双药压敏胶透皮贴剂（SIHDD-PSA）通过调节JAK-STAT信号通路具有显著的骨保护作用。SIHDD-PSA显著减轻了大鼠模型的 paw肿胀和炎症，刺激性评价证实了SIHDD-PSA的安全性。总之，这些发现为有效治疗RA提供了一种新方法，半离子氢键策略为开发透皮给药系统（TDDS）提供了新的理论基础。
