Quality by design-based optimization of teriflunomide and quercetin combinational topical transferosomes for the treatment of rheumatoid arthritis

IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY
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Abstract

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease. Combination therapy is anticipated to surpass monotherapy by targeting multiple pathways involved in RA progression. The present aim is to develop a combination of Teriflunomide (TFD) and Quercetin (QCN) loaded transferosomal gel to enhance permeability and achieve localized delivery to joint tissues. TFD or QCN transferosomes were optimized employing a 3-level, 3-factorial design Box-Behnken design (BBD). The transferosomes exhibited sustained in-vitro drug release. The topical combination gel underwent thorough evaluation of rheology, and also ex-vivo studies showed enhanced permeability through rat skin. The synergistic combination of TFD and QCN effectively suppressed NO, TNF-α and IL-6 levels in in-vitro RAW 264.7 cells. The cytotoxicity in HaCaT cell lines indicates non-toxicity of the gel, further confirmed by skin irritation study conducted in rats. The in-vivo anti-arthritic activity was evaluated in complete freund’s adjuvant induced rat paw edema model illustrates the effectiveness of the combination transferosomal gel compared to other treatment groups. In conclusion, the topical delivery of TFD and QCN combination transferosomal gel demonstrated anti-arthritic activity through localized delivery whichallows for dose reduction, thereby may reduce the systemic drug exposure and mitigate the side effects associated with oral administration of TFD.
基于设计的特立氟胺和槲皮素组合外用转移体的质量优化,用于治疗类风湿性关节炎
类风湿性关节炎(RA)是一种免疫介导的炎症性疾病。通过靶向参与类风湿关节炎进展的多种途径,联合疗法有望超越单一疗法。本研究旨在开发一种特立氟胺(TFD)和槲皮素(QCN)负载型转运体凝胶组合,以增强渗透性并实现向关节组织的局部给药。采用 3 级 3 因子设计方框-贝肯设计(BBD)对 TFD 或 QCN 转运体进行了优化。转移体在体外表现出持续的药物释放。对外用组合凝胶的流变性进行了全面评估,体内外研究也显示其在大鼠皮肤中的渗透性有所提高。TFD 和 QCN 的协同组合能有效抑制体外 RAW 264.7 细胞中的 NO、TNF-α 和 IL-6 水平。对 HaCaT 细胞系的细胞毒性表明凝胶无毒性,对大鼠皮肤的刺激性研究进一步证实了这一点。在完全弗伦德佐剂诱导的大鼠爪水肿模型中对体内抗关节炎活性进行了评估,结果表明与其他治疗组相比,转运体凝胶组合具有很好的疗效。总之,局部给药的 TFD 和 QCN 组合转运体凝胶通过局部给药显示了抗关节炎活性,从而可以减少剂量,减少全身药物暴露,减轻与口服 TFD 相关的副作用。
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来源期刊
CiteScore
10.70
自引率
8.60%
发文量
951
审稿时长
72 days
期刊介绍: The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.
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