[Cationic liposomes enhance the inhibitory effects of antisense oligodeoxynucleotide on hepatitis B virus].
OBJECTIVE
To study the interaction between 3beta-[N-(N', N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-chol), a cationic lipid, and antisense oligodeoxynucleotide (asODN), and the cytotoxicity to HepG(2) 2.2.15 cells and the inhibitory effects of asODN cationic liposomes on hepatitis B virus.


METHODS
Extract efficiency was used to estimate the interaction between DC-chol and asODN under different conditions; MTT was applied to examine the infection of DC-chol concentration on the cytotoxicity of treated cells; By ELISA technology, we examined the contents of HBsAg, and HBeAg in the culture medium, and evaluated the accelerate efficiency of neutral liposome and cationic liposomes to the inhibitory effects of asODN on hepatitis B virus, and the infection of charge ratio on the inhibitory effects of asODN cationic liposomes.


RESULTS
When the charge ratio >0.6, DC-chol could efficiently extract the asODN from the aqueous phase; The alkaline condition and the presence of Na(+), Cl(-) ions prevented the efficient interaction between DC-chol and the asODN; DC-chol cationic liposomes had some toxicity to HepG(2) 2.2.15 cells, at low concentration (0.84-26.94 mg x L(-1)), and the toxicity of DC/chol was linear with the concentration of DC/chol; Within 1.25-5.00 micromol x L(-1), the inhibition efficacy of asODN was correlated to its concentration; liposomes could enhance the inhibition efficacy of asODN on hepatitis B virus, and cationic liposomes could enhance much more (from 60% to 95%).


CONCLUSIONS
Surface-modified DC-chol cationic liposomes can efficiently enhance the anti-hepatitis B virus efficiency of asODN in vitro.
Yan
Wenwei
W
Department of Pharmaceutics, Peking University School of Pharmaceutical Science, Beijing 100083,China.
Qi
Xianrong
X
Wei
Lai
L
Fei
Ran
R
Wang
Yu
Y
D004305:Dose-Response Relationship, Drug; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000494:pharmacology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*
D008081:Liposomes; D020319:Oligodeoxyribonucleotides, Antisense