| Research Abstract |
Any clinically effective therapy does not exist for fulminant hepatitis. The main mechanism of hepatitis is due to the cell death of hepatocytes in the liver. In fact, various hepatitis can be suppressed by the administration of apoptosis inhibitors. However, these inhibitors do not have the specificity for hepatocytes, thus, showed various side effects in vivo. Therefore, we developed hepatocyte-specific nanoparticles composed of poly-lactic acid bearing galactose polymer (PVLA) on the surface. The nanoparticles encapsulated caspase (excutioner of apoptosis) inhibitor specifically interacted with hepatocytes and release the contents in the cytosol for longer period, i.e., more than 24 h compared to the control (1 h). As a result, this type of nanoparticles efficiently suppressed the Fas-mediated and IFN-gamma-mediated hepatocyte cell death in vitro. In addition, these nanoparticles also inhibited the T-cell mediated mouse hepatitis, which is thought to be a typical model of human virus hepatitis, in vivo. In vivo, the nanoparticles specifically accumulated in the hepatocytes of the liver. These particles did not accumulate in other organs. These particles showed the organ specificity and elongated effective period.
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