Targeted delivery of hyaluronic acid nanomicelles to hepatic stellate cells in hepatic fibrosis rats

作     者：Wenhao Li Chuchu Zhou Yao Fu Tijia Chen Xing Liu Zhirong Zhang Tao Gong Wenhao Li;Chuchu Zhou;Yao Fu;Tijia Chen;Xing Liu;Zhirong Zhang;Tao Gong

作者机构：Key Laboratory of Drug-Targeting and Drug Delivery System of the Education MinistrySichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610064China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2020年第10卷第4期

页      面：693-710页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 100602[医学-中西医结合临床] 

基　　金：financially supported by National Natural Science Foundation of China(81673359) Sichuan Major Science and Technology Project on Biotechnology and Medicine(No.2018SZDZX0018,China). 

主　　题：Nanomicelles Hyaluronic acid Hepatic stellate cells Hepatic fibrosis Silibinin 

摘      要：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.