ANTI-HBV EFFECT OF GALACTOSIDES MODIFIED LAMIVUDINE TARGETED TO LIVER / 解放军医学杂志

ABSTRACT

The aim of the present study was to investigate the inhibitory effect of galactosides modified lamivudine (LA) on hepatitis B virus (HBV) and examine the liver targeting ability of lamivudine modified by galactosides in vitro and in vivo (mice). Lamivudine nanoparicles modified by galactosides (LAP GSLN) were prepared and delivered into 2.2.15 cells. After 10 days, hepatitis virus B e antigen (HBeAg) expression in 2.2.15 cells was detected by ELISA, and immune fluorescence levels of HBV DNA in the medium were examined by quantitative polymerase chain reaction (PCR). The cytotoxicity of LAP GSLN on 2.2.15 cells was observed as well. In the in vivo experiment, ten male mice were randomly divided into 2 groups lap GSLN group (i.v.injection of LAP GSLN) and LA group (i.v.injection of LA). Lamivudine levels in serum, hepatic, renal, pulmonary, and splenic tissues were detected by reversed phase high performance liquid chromatography (RP HPLC). On the 6th day, the expression of HBeAg was found inhibited by LPA GSLN. HBV DNA replication was also inhibited by LAP GSLN on the 4th day. Hepatic LAP GSLN concentrations in LAP GSLN group were 3.3 fold higher that of the LA group. The above results suggested galactosides modified lamivudine could effectively inhibit the antigen expression and DNA replication of HBV, and it showed a high liver targeting ability in vivo .