| 초록 |
Acetaminophen (APAP) overdose cause acute liver failure, which consequentially increase reactive oxygen species (ROS). Overproduced ROS activates hepatic stellate cells, increases collagen expression and damages adjacent cells. Superoxide dismutase (SOD) has been investigated as ROS suppressor. However, there are limitations for oral administration of SOD such as poor absorption and enzymatic degradation. Deoxycholic acid-modified polyethylenimine (DA3) was used in this study, which can interact with bile acid transporters and liver. DA3/SOD nanoparticles showed enhanced colloidal stability and efficiently protected SOD from proteases. After DA3/SOD delivery, reduced cellular ROS level and inhibition of cell apoptosis was observed. Moreover, orally administered DA3/SOD was efficiently accumulated in the liver and reduced oxidative damage in APAP-induced mouse model. These results suggest this formulation has potency for oral delivery of protein therapeutics in hepatic failure. |
