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智能刺激响应型透皮给药系统的研制及其在治疗类风湿关节炎中高效传递布洛芬的应用。

Development of an intelligent, stimuli-responsive transdermal system for efficient delivery of Ibuprofen against rheumatoid arthritis.

机构信息

Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan.

Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan; Hamdard Institute of Pharmaceutical Sciences, Hamdard University Islamabad Campus, Islamabad, Pakistan.

出版信息

Int J Pharm. 2021 Dec 15;610:121242. doi: 10.1016/j.ijpharm.2021.121242. Epub 2021 Oct 28.

Abstract

The present study aimed to fabricate and evaluate the therapeutic efficacy of pH-responsive Ibuprofen (IB) nanoparticles (NPs) loaded transdermal hydrogel against rheumatoid arthritis (RA). The IB loaded Eudragit® L 100 (EL 100) nanoparticles were formulated through a modified nanoprecipitation technique and optimized using central composite design software. The optimized NPs were loaded into Carbopol® 934-based hydrogel by solvent evaporation method and were analyzed for physicochemical characteristics. The mean particle size of the prepared NPs was 48 nm with an entrapment efficiency of 90%. The transdermal hydrogel showed a pH-responsive sustained drug release and high penetration through the skin. Moreover, the prepared nanocarrier system exhibited therapeutic efficacy at inflamed joints' sites both in acute and chronic RA mice model. The therapeutic efficacy of the prepared formulation was confirmed through the results of various behavioral, biochemical, and cytokines-based assays. Similarly, the assessment of histopathological and radiological images, as well as the skin irritation studies further strengthens the potential use of the prepared formulation through the transdermal route. The current findings suggested that IB loaded pH-responsive NPs based transdermal hydrogel can be used as an efficient agent to manage RA.

摘要

本研究旨在制备并评估 pH 响应型布洛芬(IB)纳米粒子(NPs)负载透皮水凝胶治疗类风湿关节炎(RA)的疗效。通过改良的纳米沉淀技术制备 IB 负载 Eudragit® L 100(EL 100)纳米粒子,并使用中心组合设计软件对其进行优化。将优化后的 NPs 通过溶剂蒸发法载入 Carbopol® 934 基水凝胶中,并对其理化特性进行分析。所制备的 NPs 的平均粒径为 48nm,包封效率为 90%。所制备的透皮水凝胶具有 pH 响应性的持续药物释放和高皮肤穿透性。此外,所制备的纳米载体系统在急性和慢性 RA 小鼠模型中均在发炎关节部位表现出治疗效果。通过各种行为、生化和基于细胞因子的检测,证实了所制备配方的治疗效果。同样,对组织病理学和放射学图像的评估以及皮肤刺激性研究进一步通过透皮途径证实了所制备配方的潜在用途。目前的研究结果表明,IB 负载 pH 响应型 NPs 透皮水凝胶可用作治疗 RA 的有效药物。

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