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用于治疗类风湿性关节炎的甲氨蝶呤凝胶的靶向药物递送

Targeted drug delivery of Methotrexate gels for the treatment of Rheumatoid Arthritis.

作者信息

Venkatesh Madhugiri Prakash, Kumar Tegginmat Pramod, Pai Deeksha Ramananda

机构信息

Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Sri Shivarathreeshwara Nagara, Mysuru 570015, Karnataka, India.

出版信息

Saudi Pharm J. 2020 Dec;28(12):1548-1557. doi: 10.1016/j.jsps.2020.10.003. Epub 2020 Oct 22.

Abstract

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.

摘要

类风湿性关节炎(RA)被认为是一种使人衰弱的疾病,会增加严重发病和过早死亡的风险。为了规避与药物相关的毒性以及抗炎药的无效性,迫切需要一种能提高生物利用度的先进给药系统。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方法的可行性。它以泊洛沙姆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)作为共聚物进行配制,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。优化后的原位凝胶(M4)具有热响应性,在96小时时释放93.26±2.39%的MTS。此外,MTS在优化后的无菌且可注射的原位凝胶中分布均匀。对Wistar大鼠的体内研究表明,在28天的研究期间爪部水肿大幅减轻,并且与注射部位的组织具有生物相容性。该研究成功配制并优化了用于类风湿性关节炎有效治疗的MTS原位凝胶。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e997/7783075/17ad286b4303/gr1.jpg

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