| 초록 |
Liver cirrhosis is a chronic liver disease which is characterized by the activation of hepatic stellate cells (HSCs), the fibrotic tissue formation, and the liver malfunction. HSCs play important roles in the progress of liver cirrhosis and TGF-β is a well-known cytokine related to the tissue fibrosis. In this work, a target specific systemic delivery system of siRNA therapeutics was successfully developed using reducible polyethyleneimine grafted hyaluronic acid [(PEI-SS)-g-HA] conjugates. After in vitro gene silencing tests, systemic delivery of apolipoprotein B (ApoB) siRNA/(PEI-SS)-g-HA complex was carried out, which resulted in a drastically reduced ApoB mRNA level. Finally, TGF-β siRNA/(PEI-SS)-g-HA complex showed a feasible therapeutic effect on liver cirrhosis with a significantly reduced nodule formation, collagen content, and HSC number. The siRNA/(PEI-SS)-g-HA complex can be exploited for the target specific systemic treatment of various liver diseases. |
