Ding Chengbiao, Liu Zhenyu, Mei Lin, Wei Juan, Liu Qi, Ouyang Wenchong, Dong Zhimian, Yang Runhuai, Wu Zhengwei, Feng Xiaojun
Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province 230601, China.
ACS Omega. 2025 Aug 17;10(33):37330-37341. doi: 10.1021/acsomega.5c02934. eCollection 2025 Aug 26.
Rheumatoid arthritis (RA), an autoimmune disease, severely impairs joint function and mobility, causing pain, stiffness, and joint deformity. As an active ingredient of ancient herbs and a widely studied polyphenol flavonoid glycoside, quercetin has a historical use in the treatment of rheumatoid arthritis. However, its low oral bioavailability and potential carcinogenic effects limit its systemic use. Therefore, we propose an injectable hydrogel-based targeted drug delivery system designed to respond to the pathological environment of rheumatoid arthritis joints. This system controls the release of anti-inflammatory drugs to promote joint repair. Low-temperature atmospheric plasma (LTAP), characterized by high-energy properties, activates the bioactivity of natural polyphenols.Utilizing LTAP to stimulate quercetin into protocatechuic acid, we prepared an efficacious gel system by dynamically coupling with poloxamer and sodium alginate. This organic gel maintains typical hydrogel properties of viscosity, biosafety, and temperature sensitivity. Compared with quercetin alone, this activated organic gel offers enhanced safety, absorption, and metabolism. In vivo studies have demonstrated that local injection of this hydrogel effectively reduces bone destruction, inhibits pannus formation, and significantly suppresses inflammatory factors such as IL-6, IL-1β, and TNF-α, thereby protecting joints.
类风湿性关节炎（RA）是一种自身免疫性疾病，会严重损害关节功能和活动能力，导致疼痛、僵硬和关节畸形。槲皮素作为一种古老草药的活性成分和一种经过广泛研究的多酚类黄酮糖苷，在历史上曾用于治疗类风湿性关节炎。然而，其口服生物利用度低以及潜在的致癌作用限制了它的全身应用。因此，我们提出了一种基于可注射水凝胶的靶向药物递送系统，该系统旨在响应类风湿性关节炎关节的病理环境，控制抗炎药物的释放以促进关节修复。低温常压等离子体（LTAP）具有高能特性，可激活天然多酚的生物活性。利用LTAP将槲皮素刺激转化为原儿茶酸，我们通过与泊洛沙姆和海藻酸钠动态偶联制备了一种有效的凝胶系统。这种有机凝胶保持了粘度、生物安全性和温度敏感性等典型水凝胶特性。与单独使用槲皮素相比，这种活化的有机凝胶具有更高的安全性、吸收性和代谢性。体内研究表明，局部注射这种水凝胶可有效减少骨质破坏，抑制血管翳形成，并显著抑制白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）等炎症因子，从而保护关节。
