Intra-articular injection of indomethacin-methotrexate in situ hydrogel for the synergistic treatment of rheumatoid arthritis.,Journal of Materials Chemistry B

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Intra-articular injection of indomethacin-methotrexate in situ hydrogel for the synergistic treatment of rheumatoid arthritis.
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-01-13 , DOI: 10.1039/c9tb01795j
Na Yin ₁ , Xueting Guo ₁ , Rong Sun ₁ , Hongbing Liu ₁ , Lihua Tang ₁ , Jingxin Gou ₁ , Tian Yin ₂ , Haibing He ₁ , Yu Zhang ₁ , Xing Tang ₁

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Rheumatoid arthritis is a chronic systemic autoimmune disease that causes joint swelling and cartilage damage. The objective of the present work was to develop a temperature-sensitive hydrogel (D-NGel) containing nanoparticles (D-NPs), which could simultaneously deliver combination indomethacin and methotrexate. D-NPs were formed by multiple non-covalent interactions between PEI-SS and the carboxyl-containing hydrophobic small molecule drugs IND and MTX, which were then loaded into a temperature-sensitive hydrogel matrix. The Tsol/gel of the temperature-sensitive hydrogel matrix composed of 27% F127 and 10% F68 was 33 °C and the gelation time was less than 15 s. The resultant D-NGel was injected into the articular cavity of collagen-induced arthritis rats and quickly transformed in situ into gels which slowly released drug in the joint fluid for up to 72 h. The D-NGel effectively reduced joint swelling, bone erosion and expression of inflammatory cytokines in the ankle fluid and knee joint fluid. In addition, liver and kidney function tests and histopathological examination indicated there was a good biological safety for D-NGel. In conclusion, this work has demonstrated the great potential of the D-NGel for sustained co-delivery of IND and MTX for the synergistic treatment of rheumatoid arthritis, treating both the symptoms and the root causes of rheumatoid arthritis.

中文翻译：

关节内注射吲哚美辛-甲氨蝶呤原位水凝胶用于类风湿关节炎的协同治疗。

类风湿关节炎是一种慢性全身性自身免疫性疾病，会导致关节肿胀和软骨损伤。本工作的目的是开发一种含有纳米颗粒（D-NPs）的温度敏感型水凝胶（D-NGel），它可以同时递送消炎痛和甲氨蝶呤的组合。D-NP是由PEI-SS与含羧基的疏水性小分子药物IND和MTX之间的多次非共价相互作用形成的，然后将其加载到对温度敏感的水凝胶基质中。由27％F127和10％F68组成的热敏性水凝胶基质的Tsol /凝胶为33°C，胶凝时间小于15 s。将生成的D-NGel注射到胶原诱导的关节炎大鼠的关节腔中，并迅速原位转化为凝胶，该凝胶在关节液中缓慢释放药物长达72小时。D-NGel可有效减少踝关节和膝关节液中的关节肿胀，骨侵蚀和炎性细胞因子的表达。此外，肝肾功能检查和组织病理学检查表明，D-NGel具有良好的生物学安全性。总而言之，这项工作证明了D-NGel在IND和MTX的持续联合给药中具有巨大的潜力，可以协同治疗类风湿关节炎，治疗类风湿关节炎的症状和根本原因。骨侵蚀以及踝液和膝关节液中炎性细胞因子的表达。此外，肝肾功能检查和组织病理学检查表明，D-NGel具有良好的生物学安全性。总而言之，这项工作证明了D-NGel在IND和MTX的持续联合给药中具有巨大的潜力，可以协同治疗类风湿关节炎，治疗类风湿关节炎的症状和根本原因。骨侵蚀以及踝液和膝关节液中炎性细胞因子的表达。此外，肝肾功能检查和组织病理学检查表明，D-NGel具有良好的生物学安全性。总而言之，这项工作证明了D-NGel在IND和MTX的持续联合给药中具有巨大的潜力，可以协同治疗类风湿关节炎，治疗类风湿关节炎的症状和根本原因。

更新日期：2020-02-13

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