Curcumin- and Cyclopamine-Loaded Liposomes to Enhance Therapeutic Efficacy Against Hepatic Fibrosis.
Curcumin- and Cyclopamine-Loaded Liposomes to Enhance Therapeutic Efficacy Against Hepatic Fibrosis.
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负载姜黄素和环巴胺的脂质体增强抗肝纤维化的治疗效果”已被《药物设计、开发和治疗》接受发表
DOI：
10.2147/dddt.s287442
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Fei X
中科院分区：
文献类型：
--
作者：
Zhang T;Li Y;Song Y;Chen X;Li J;Peng Q;He J;Fei X
肝纤维化是一个公共卫生问题，其特征是肝星状细胞（HSC）的激活，引发细胞外基质（ECM）的过度产生。抑制 HSC 活化可能是一种有效的治疗方法。由于多种途径控制 HSC 激活，具有不同机制的药物组合可能比单一疗法更有效。在这里，我们制备了负载姜黄素和环杷明的脂质体来抑制 HSC 活化。我们系统地分析了两种药物脂质体的理化特性，以及它们在基因、蛋白质和细胞水平上对HSC增殖、活化和胶原蛋白产生的影响。制备的脂质体有助于溶解这两种药物，有助于细胞吸收它们。与溶液中两种药物的自由组合或单独负载任一药物的脂质体相比，负载两种药物的脂质体抑制细胞增殖、迁移和侵袭，并且诱导更多的细胞凋亡并扰乱细胞周期。载有两种药物的脂质体强烈抑制 HSC 活化和胶原蛋白分泌。我们的结果表明，脂质体封装可以增加姜黄素和环杷明的摄取以及它们在抗纤维化方面的协同作用。这种方法显示出治疗肝纤维化的潜力。
Hepatic fibrosis is a public health problem characterized by activation of hepatic stellate cells (HSCs), which triggers excessive production of extracellular matrix (ECM). Inhibition of HSC activation may be an effective treatment. Since various pathways control HSC activation, a combination of drugs with different mechanisms may be more effective than monotherapy. Here, we prepared liposomes loaded with curcumin and cyclopamine to inhibit HSC activation. We systematically analyzed the physicochemical characteristics of liposomes loaded with the two drugs, as well as their effects on HSC proliferation, activation and collagen production on gene, protein and cellular levels. The prepared liposomes helped solubilize both drugs, contributing to their uptake by cells. Liposomes loaded with both drugs inhibited cell proliferation, migration and invasion, as well as induced more apoptosis and perturbed the cell cycle more than the free combination of both drugs in solution or liposomes loaded with either drug alone. Liposomes loaded with both drugs strongly suppressed HSC activation and collagen secretion. Our results suggest that liposome encapsulation can increase the uptake of curcumin and cyclopamine as well as the synergism between them in anti-fibrosis. This approach shows potential for treating hepatic fibrosis.