[Study on the hepatocytic cell targetability of liposomes].
OBJECTIVE
To target for hepatocytic cell, liposomes was modified by special ligand.


METHODS
Sterically stabilized liposomes (SSL) was conjugated with asialofeticin (AF), the ligand of asialoglycoprotein receptor (ASGP-R) of hepatocyte. ASGP-R-BLM is the ASGP-R reconstructed on bilayer lipid membrane (BLM). The recognition reaction between AF-SSL and ASGP-R-BLM can be monitored by the varieties of membrane electrical parameters. The targetability of AF-SSL mediated to hepatocyte was detected by radioisotopic labeled in vitro and in vivo. The therapeutic effect of antihepatocarcinoma was observed also.


RESULTS
The lifetime of ASGP-R-BLM decreased with the added amount of AF-SSL. It was demonstrated that there was recognition reaction between AF-SSL and ASGP-R-BLM. The combination of AF-SSL with hepatocyte was significantly higher than that of SSL without AF-modified in vitro and in vivo. The survival time of rat for AF-SSL carriered ADM (adriamycin) group was much longer and the toxicities on heart, kidney and lung were lower than those SSL carried ADM group.


CONCLUSIONS
It is possible to actively target the cell with specific receptor by ligand modified liposomes. The result prvide scientific basis of hepatocyte targeted liposomes.
Hou
Xin-pu
XP
Department of Pharmaceutics, School of Pharmacy, Peking University, Beijing 100083, China. houxinpu@mail.bjmu.edu.cn
Wang
Li
L
Wang
Xiang-tao
XT
Li
Sha
S
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers; D016503:Drug Delivery Systems; D060748:Fetuins; D022781:Hepatocytes / Q000378:metabolism*; D008024:Ligands; D008051:Lipid Bilayers; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy; D008297:Male; D051379:Mice; D011897:Random Allocation; D051381:Rats; D000509:alpha-Fetoproteins / Q000737:chemistry
D000970:Antineoplastic Agents; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D004337:Drug Carriers; D060748:Fetuins; D008024:Ligands; D008051:Lipid Bilayers; D008081:Liposomes; D000509:alpha-Fetoproteins; C017029:asialofetuin; D004317:Doxorubicin