Hepatic fibrosis is one kind of liver diseases with a high mortality rate and incidence. The activation and proliferation of hepatic stellate cells (HSCs) is the most fundamental reason of hepatic fibrosis. There are no specific and effective drug delivery carriers for the treatment of hepatic fibrosis at present. We found that when hepatic fibrosis occurs, the expression of CD44 receptors on the surface of HSCs is significantly increased. Based on this finding, we designed silibinin-loaded hyaluronic acid (SLB-HA) micelles to achieve the treatment of hepatic fibrosis. Meanwhile, we constructed liver fibrosis rat model using Sprague-Dawley rats. We demonstrated that HA micelles had specific uptake to HSCs in vitro while avoiding the distribution in normal liver cells and the phagocytosis of macrophages. Importantly, HA micelles showed a significant liver targeting effect in vivo, especially in fibrotic liver which highly expressed CD44 receptors. In addition, SLB-HA micelles could selectively kill activated HSCs, having an excellent anti-hepatic fibrosis effect in vivo and a significant sustained release effect, and also had a good biological safety and biocompatibility. Overall, HA micelles represented a novel nanomicelle system which showed great potentiality in anti-hepatic fibrosis drugs delivery.

中文翻译：

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透明质酸纳米胶束向肝纤维化大鼠肝星状细胞的靶向递送。

肝纤维化是一种死亡率高，发病率高的肝病。肝星状细胞（HSC）的激活和增殖是肝纤维化的最根本原因。目前尚无用于治疗肝纤维化的特异性和有效的药物递送载体。我们发现，当发生肝纤维化时，HSCs表面的CD44受体表达显着增加。基于此发现，我们设计了负载水飞蓟宾的透明质酸（SLB-HA）胶束，以实现肝纤维化的治疗。同时，我们使用Sprague-Dawley大鼠构建了肝纤维化大鼠模型。我们证明HA胶束在体外具有对HSC的特异性摄取，同时避免了在正常肝细胞中的分布和巨噬细胞的吞噬作用。重要的，HA胶束在体内表现出显着的肝靶向作用，尤其是在高度表达CD44受体的纤维化肝中。此外，SLB-HA胶束可以选择性地杀死活化的HSC，在体内具有优异的抗肝纤维化作用和显着的持续释放作用，还具有良好的生物学安全性和生物相容性。总体而言，HA胶束代表了一种新型的纳米胶束系统，在抗肝纤维化药物的输送中显示出巨大的潜力。