| 초록 |
Target specific systemic delivery systems of siRNA have been successfully developed using hyaluronic acid (HA) reducible polyethyleneimine (PEI) conjugates. Non-toxic low molecular weight PEI (MW = 2 kDa) was crosslinked with cystamine bisacrylamide to prepare reducible PEI-SS in the body. Then, PEI-SS was conjugated with HA in the form of graft-copolymers to enhance serum stability and facilitate target specific delivery of siRNA by HA receptor mediated endocytosis. The siRNA/(PEI-SS)-HA complex exhibited an excellent in vitro gene silencing efficiency in the range of 50~80% in the absence and presence of 50 vol% serum. After tail-vein injection, apolipoprotein B siRNA/(PEI-SS)-b-HA complex resulted in the drastic reduction of apolipoprotein B mRNA level down to 80%. Moreover, TGF siRNA/(PEI-SS)-g-HA complex demonstrated a feasible therapeutic effect on the treatment of cirrhotic model mice. |
