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微乳介导的甲氨蝶呤水凝胶有效递送:银屑病治疗中的一大壮举。

Microemulsions mediated effective delivery of methotrexate hydrogel: more than a tour de force in psoriasis therapeutics.

作者信息

Amarji Basant, Garg Neeraj K, Singh Bhupinder, Katare Om Prakash

机构信息

a Drug Delivery Research Group , University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University , Chandigarh , India and.

b UGC Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites (Biomedical Sciences), Panjab University , Chandigarh , India.

出版信息

J Drug Target. 2016;24(2):147-60. doi: 10.3109/1061186X.2015.1058804. Epub 2015 Jul 23.

Abstract

Methotrexate (MTX), a well known drug for the treatment of cancer and rheumatoid arthritis, has gained prominence in the treatment of psoriasis over the period of years. However, the present mode of systemic administration through oral or parenteral route has always proposition, full of compromises. The toxicity of drug to the vital organs and physiological environment is the major concern. Also, its poor skin penetration is one major problem. Hence novel system based on lipid carriers has been considered here to overcome the barriers. Microemulsions (MEs) were prepared using pseudo-ternary phase diagram (PTPD) and they were characterized for various parameters such as size, shape (cryo-SEM), PDI, zeta potential, etc. The chosen MEs system (optimized) was then incorporated into secondary vehicles and characterized for rheological behavior, texture profile analysis, in vitro release, ex vivo permeation and drug distribution into different layers of skin. The developed formulations were further evaluated in ex vivo and in vivo such as cell line study, imiquimod-induced psoriatic model, allergic contact dermatitis, rat tail model (% orthokeratosis) and safety test (Draize test). The MEs based MTX gel has shown its potential in locating the drug at the desired domain of stratum corneum, epidermal and dermal layers of skin and reducing systemic absorption. Our results are suggestive of MEs potential as a novel carrier for topical delivery of MTX in topical therapeutic and safety approaches. In conclusion, developed MEs-based hydrogel has shown promising results in achieving effective delivery of MTX.

摘要

甲氨蝶呤(MTX)是一种治疗癌症和类风湿性关节炎的知名药物,多年来在银屑病治疗中受到关注。然而,目前通过口服或肠胃外途径进行全身给药的方式一直存在诸多问题,充满了妥协之处。药物对重要器官和生理环境的毒性是主要担忧。此外,其皮肤渗透性差也是一个主要问题。因此,本文考虑采用基于脂质载体的新型系统来克服这些障碍。利用伪三元相图(PTPD)制备了微乳(MEs),并对其粒径、形状(低温扫描电子显微镜)、多分散指数(PDI)、ζ电位等各种参数进行了表征。然后将选定的MEs系统(优化后)加入二级载体中,并对其流变行为、质地剖面分析、体外释放、离体渗透以及药物在皮肤不同层中的分布进行了表征。所开发的制剂进一步在离体和体内进行了评估,如细胞系研究、咪喹莫特诱导的银屑病模型、过敏性接触性皮炎、大鼠尾部模型(正角化病百分比)和安全性测试(Draize试验)。基于MEs的MTX凝胶已显示出将药物定位在角质层、表皮和真皮层所需部位并减少全身吸收的潜力。我们的结果表明MEs作为MTX局部递送的新型载体在局部治疗和安全性方面具有潜力。总之,所开发的基于MEs的水凝胶在实现MTX的有效递送方面显示出了有前景的结果。

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