Preparation and property analysis of a hepatocyte targeting pH-sensitive liposome.
OBJECTIVE
To develop a hepatocyte targeting pH-sensitive liposome for drug delivery based on active targeting technology mediated by asialoglycoprotein receptors.


METHODS
Four types of targeting molecules with galactose residue were synthesized and mixed with pH-sensitive lipids DC-chol/DOPE to prepare liposome with integrated property of hepatocyte specificity and pH sensitivity. Liposome 18-gal was selected with the best transfection activity through cellular uptake experiment. Property analysis was made through experiments of competitive inhibition of receptors, red blood cell hemolysis, in vitro cytotoxicity test by MTS assay and mediation of inhibitory effects of antisense phosphorothioate ODN on gene expression, etc.


RESULTS
Liposome 18-gal had the desired properties of hepatocyte specificity, pH sensitivity, low cytotoxicity, and high transfection efficiency.


CONCLUSIONS
Liposome 18-gal can be further developed as a potential hepatocyte- targeting delivery system.
Wen
Si-Yuan
SY
Beijing Institute of Radiation Medicine, Beijing 100850, China.
Wang
Xiao-Hong
XH
Lin
Li
L
Guan
Wei
W
Wang
Sheng-Qi
SQ
D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000493:pharmacokinetics* / Q000633:toxicity; D008113:Liver Neoplasms; D009841:Oligonucleotides / Q000493:pharmacokinetics; D010957:Plasmids / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D014162:Transfection / Q000379:methods*
D008081:Liposomes; D009841:Oligonucleotides