期刊
ACTA BIOMATERIALIA
卷 116, 期 -, 页码 356-367出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2020.09.014
关键词
Reactive Oxygen Species (ROS); Liver fibrosis; Chitosan Nanoparticles; Bilirubin; Losartan
资金
- Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Korean government (MSIT) [2019M3E5D1A02068082]
The development of nanoparticles that can be used as stimuli-responsive drug carriers for the treatment of different diseases has been an emerging area of research. In this study, we designed a chitosan-bilirubin micelle (ChiBil) carrying losartan, which is responsive to intrinsic reactive oxygen species (ROS), for the treatment of hepatic fibrosis. Because bilirubin is hydrophobic in nature, its carboxyl group was conjugated to an amine group from chitosan using EDC-NHS chemistry to form an amphiphilic conjugate, ChiBil. Losartan is an angiotensin receptor blocker that reduces hepatic fibrosis, and it was used as the therapeutic payload in this study to form ChiBil-losartan micelles. The release characteristics of ChiBil-losartan were tested by ROS generation to confirm losartan release. Human hepatic stellate cell line LX2 was found to be the best in vitro model for the study. The reduction of hepatic stellate cell activation after treatment with ChiBil-losartan was analyzed based on the expression of alpha-smooth muscle actin (alpha-SMA) in both in vitro and in vivo studies. Advanced liver fibrosis was induced in C3H/HeN mice using a thioacetamide (TAA) via intraperitoneal injection and 10% ethanol (EtOH) in their drinking water. In addition, the hydroxyproline levels, histopathological evaluation, and mRNA quantification in the liver showed a decreased collagen content in the treated groups compared to that in the untreated control group. Macrophage infiltration studies and qPCR studies of inflammatory markers also proved the reduction of hepatic fibrosis in the treatment group. The intravenous administration of ChiBil-losartan resulted in decreased fibrosis in a TAA/EtOH-induced liver fibrosis mouse model. The in vitro and in vivo results suggest that the ROS stimuli-responsive ChiBil nanoparticles carrying losartan may be a potent therapeutic option for the treatment of hepatic fibrosis. The combined effect of losartan and bilirubin exhibited a decreased hepatic fibrosis both in vitro and in vivo. (C) 2020 Published by Elsevier Ltd on behalf of Acta Materialia Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据