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 while avoiding the distribution in normal liver cells and the phagocytosis of macrophages. Importantly, HA micelles showed a significant liver targeting effect , 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 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.
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| http://dx.doi.org/10.1016/j.apsb.2019.07.003 | DOI Listing |
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