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环孢菌素阳离子脂质体的制备、表征及治疗银屑病的评价。

Preparation, characterization, and evaluation of cyclosporine cationic liposomes for the treatment of psoriasis.

机构信息

National Institute of Pharmaceutical Education and Research Hyderabad, Hyderabad, India.

出版信息

J Liposome Res. 2020 Mar;30(1):68-79. doi: 10.1080/08982104.2019.1593449. Epub 2019 Apr 23.

Abstract

Cyclosporine (CYC), a calcineurin inhibitor acts specifically on T-cells and is one of the most effective treatment options for psoriasis. Systemic administration of the drug has been associated with dose-dependent toxic effects, while its topical delivery is a challenging task due to unfavourable physicochemical properties of drug. The aim of the present study is to develop and evaluate the efficacy of topical liposomal gel containing CYC loaded cationic liposomal nanocarriers in imiquimod induced psoriatic plaque model. Liposomes composed of DOTAP and cholesterol was formulated by different liposomal preparation techniques. Optimized liposomal carriers prepared by ethanol injection method were characterized with respect to size, zeta potential, entrapment efficiency, stability, drug release and studies. Cationic liposomes with particle size of 111 ± 1.62 nm, PDI of 0.27 ± 0.08, entrapment efficiency of 93 ± 2.12%, and zeta potential of 41.12 ± 3.56 mV were obtained. Drug loaded liposomal gels showed shear thinning behaviour, which is suitable for topical application. Topical application of CYC liposomal gels on imiquimod induced psoriatic plaque model reduced the symptoms of psoriasis and levels of key psoriatic cytokines such as tumour necrosis factor-α, IL-17, and IL-22. In conclusion, the developed liposomal carrier of CYC was found to be effective and can find application in treatment of psoriasis.

摘要

环孢素(CYC)是一种钙调神经磷酸酶抑制剂,特异性作用于 T 细胞,是治疗银屑病最有效的方法之一。该药物的全身给药与剂量依赖性毒性作用有关,而其局部给药由于药物的不良理化性质而成为一项具有挑战性的任务。本研究旨在开发和评估载环孢素的阳离子脂质体纳米载体的局部脂质体凝胶的疗效,该纳米载体负载于阳离子脂质体纳米载体中。由 DOTAP 和胆固醇组成的脂质体通过不同的脂质体制备技术进行配方。通过乙醇注入法制备的优化脂质体载体在大小、Zeta 电位、包封效率、稳定性、药物释放和研究方面进行了特征描述。阳离子脂质体的粒径为 111±1.62nm、PDI 为 0.27±0.08、包封效率为 93±2.12%、Zeta 电位为 41.12±3.56mV。载药脂质体凝胶表现出剪切稀化行为,适合于局部应用。将 CYC 脂质体凝胶局部应用于咪喹莫特诱导的银屑病斑块模型可减轻银屑病的症状,并降低关键银屑病细胞因子(如肿瘤坏死因子-α、IL-17 和 IL-22)的水平。总之,所开发的 CYC 脂质体载体被证明是有效的,并可应用于治疗银屑病。

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