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Targeted drug delivery of Methotrexate in situ gels for the treatment of Rheumatoid Arthritis
Saudi Pharmaceutical Journal ( IF 4.1 ) Pub Date : 2020-10-22 , DOI: 10.1016/j.jsps.2020.10.003
Madhugiri Prakash Venkatesh 1 , Tegginmat Pramod Kumar 1 , Deeksha Ramananda Pai 1
Affiliation  

Rheumatoid arthritis (RA) is considered a debilitating disease that increases the risk of significant morbidity and premature mortality. To circumvent drug-related toxicity and ineffectiveness of anti-inflammatory drugs, there is a significant need for an advanced delivery system that increases bioavailability. The feasibility of in situ gel of methotrexate sodium (MTS) as an effective management for Rheumatoid arthritis was investigated. It was formulated with pluronic F-127 (PLF-127) as primary polymer, hydroxypropyl methylcellulose K4M (HK4M), and polycarbophil (PCL) as a copolymer and characterized by various parameters. The efficacy evaluation by Freund's complete adjuvant (FCA) model, biocompatibility assessment by histopathological studies conducted. The optimized in situ gel (M4) was thermoresponsive, released 93.26 ± 2.39% MTS at 96 hours. In addition, distribution of MTS was even in the optimized sterile and syringeable in situ gel. In vivo studies on wistar rats demonstrated a substantial reduction in paw oedema during the 28-day study period and were biocompatible with the tissues at the injection site. The study was successful in formulating, optimizing MTS in situ gel for effective management of RA.



中文翻译:

甲氨蝶呤原位凝胶靶向给药治疗类风湿关节炎

类风湿性关节炎 (RA) 被认为是一种使人衰弱的疾病,会增加显着发病率和过早死亡的风险。为了规避与药物相关的毒性和抗炎药的无效性,迫切需要一种提高生物利用度的先进递送系统。研究了甲氨蝶呤钠 (MTS) 原位凝胶作为类风湿性关节炎有效治疗的可行性。它由 pluronic F-127 (PLF-127) 作为主要聚合物、羟丙基甲基纤维素 K4M (HK4M) 和聚卡波非 (PCL) 作为共聚物配制而成,并通过各种参数进行表征。通过弗氏完全佐剂(FCA)模型进行疗效评估,通过组织病理学研究进行生物相容性评估。优化的原位凝胶 (M4) 具有热响应性,释放量为 93.26 ± 2。39% MTS 在 96 小时。此外,MTS 的分布甚至在优化的无菌和可注射原位凝胶中。对 wistar 大鼠的体内研究表明,在 28 天的研究期间,足爪水肿显着减少,并且与注射部位的组织具有生物相容性。该研究成功地配制和优化了 MTS 原位凝胶,以有效管理 RA。

更新日期:2020-12-29
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