类风湿性关节炎(RA),一种免疫介导的炎性疾病,其特征是关节中大量浸润的免疫细胞和异常升高的活性氧(ROS)。巨噬细胞分泌的各种促炎因子和炎症细胞升高的ROS紧密交织在一起,共同导致关节损伤。RA治疗需要靶向和持续的抗炎和抗氧化策略。缓解氧化应激,靶向炎性细胞因子的来源,我们开发了一种热敏可注射水凝胶,Dex-DSLip/Cro@凝胶,以协调靶向抗炎和抗氧化作用。在可注射凝胶中,地塞米松(Dex)脂质体(Dex-DSLip),用硫酸葡聚糖(DS)改性,通过与清道夫受体A(SR-A)相互作用靶向巨噬细胞。同时,crocinI(Cro)以很高的负载能力负载在凝胶中。Dex-DSLip/Cro@Gel的多孔结构成功地延长了两种药物的保留时间,并维持了Dex和Cro的释放。在RA大鼠关节内注射Dex-DSLip/Cro@Gel后,炎症因子在踝关节中的表达显著降低。关节红斑和骨侵蚀明显减轻。通过Dex和Cro的协同作用,Dex-DSLip/Cro@Gel显示了靶向抗炎和抗氧化作用,以及减轻骨侵蚀和对RA的长期治疗作用。这种热敏可注射纳米复合水凝胶可协同抗炎和抗氧化作用,并靶向关节中的微环境,为RA的治疗提供了新的途径。
Rheumatoid arthritis (RA), an immune-mediated inflammatory disease, is characterized by a large number of infiltrated immune cells and abnormally elevated reactive oxygen species (ROS) in the joint. Various proinflammatory factors secreted by macrophages and the elevated ROS by inflammatory cells are deeply intertwined and together contribute to joint damage. Targeted and sustained anti-inflammation and antioxidation strategies are needed for RA treatment. To alleviate the oxidative stress and target the source of inflammatory cytokines, we developed a thermosensitive injectable hydrogel, Dex-DSLip/Cro@Gel, to coordinate the targeted anti-inflammatory and antioxidation effects. Within the injectable gel, dexamethasone (Dex)-loaded liposomes (Dex-DSLip), modified with dextran sulfate (DS), target macrophages via interaction with scavenger receptor A (SR-A). Simultaneously, crocin I (Cro) is loaded in the gel with a high loading capacity. The porous structure of Dex-DSLip/Cro@Gel successfully prolongs the retention time of both drugs and sustains the release of Dex and Cro. After intra-articular injection of Dex-DSLip/Cro@Gel in RA rats, the expression of inflammatory factors in the ankle joints was significantly reduced. Joint erythema and bone erosion were markedly alleviated. Through the synergistic effects of Dex and Cro, Dex-DSLip/Cro@Gel demonstrates targeted anti-inflammatory and antioxidation effects as well as mitigated bone erosion and long-term therapeutic effects for RA. This thermosensitive injectable nanocomposite hydrogel synergizes anti-inflammatory and antioxidation effects and targets the microenvironment in the joint, offering a new approach for RA treatment.