类风湿性关节炎（RA）是一种严重影响关节并限制运动的慢性炎症性疾病。RA有多种治疗方案可提供短期止痛作用，但尚无长期缓解疾病的方法。显然，细胞因子在该疾病的病理生理中起着重要作用。然而，异常的免疫反应、遗传易感性、病毒感染或毒物是RA可能的致病介质。类风湿性关节炎患者的滑膜液包含细胞因子，尤其是成骨细胞生成细胞因子以及巨噬细胞集落刺激因子（M-CSF）和核转录因子-κB配体诱导物（RANKL）等侵袭因子。此外，肿瘤坏死因子-α（TNF-α）和白细胞介素（IL-1，6和17）加剧了成骨细胞的分化和活化。因此，为了限制细胞因子的表达，我们使用布地奈德作为治疗先导物，并将其封装到高度生物相容的水凝胶系统中。我们开发的水凝胶系统是酶响应性的，并能提供持续的药物释放流，时间延长。该水凝胶通过ζ-电位分析，场发射扫描电子显微镜（FE-SEM）和衰减全反射-傅里叶变换红外（ATR-FTIR）光谱分析进行表征，进一步封装了布地奈德（糖皮质激素）用于治疗目的。显然，载有布地奈德的酶响应性水凝胶相比疾病组显示了关节生理改善，并下调了炎症标志物。

Rheumatoid arthritis (RA) is a chronic inflammatory disease that severely affects joints and restricts locomotion. Various treatment regimens are available for RA, providing short-term relief from pain, but long-term relief from the disease is still not available. Evidently, cytokines play a crucial role in the pathophysiology of the disease. However, aberrant immune responses, genetic dispositions, viral infections, or toxicants are some possible causative mediators of RA. The synovial fluid of rheumatoid arthritis patients encompass cytokines, especially osteoclastogenic cytokines, and invasion factors such as macrophage colony-stimulating factor (M-CSF) and the receptor activator of NF-κB ligand (RANKL). Moreover, tumor necrosis factor-α (TNF-α) and interleukins (IL-1, 6, and 17) intensify osteoclast differentiation and activation. Therefore, in order to restrict the cytokine expression, we used budesonide as a therapeutic lead and encapsulated it into a highly biocompatible hydrogel system. The hydrogel system developed by us is enzyme-responsive and provides sustained drug release flow over an extended period of time. This hydrogel is characterized by ζ-potential analysis, field-emission scanning electron microscopy (FE-SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, and it is further encapsulated with budesonide (glucocorticoids) for therapeutic purposes. Evidently, Bud-loaded ER-hydrogel showed improvement in joint physiology compared to the disease group and downregulated the inflammatory markers.