Intracellular delivery of membrane-impermeable hydrophilic molecules to a hepatoblastoma cell line by asialoglycoprotein-labeled liposomes.

Abstract

BACKGROUND AND PURPOSE:

Mammalian hepatic receptors are specific for the terminal D-galactose of desialylated glycoproteins. This study used asialofetuin-labeled liposomes (AF-liposomes) to target hepatoma cells using this receptor mechanism, and investigated their efficiency in intracellular delivery of membrane-impermeable hydrophilic molecules to a hepatoblastoma cell line (HepG2).

METHODS:

Inulin was used as a model molecule. Blank liposomes consisting of phosphatidylcholine:phosphatidic acid:cholesterol in 6:1:6 molar ratio were prepared. Palmitoyl-asialofetuin was anchored onto the blank liposomes using a detergent dialysis method. 3H-inulin was entrapped in the AF-liposomes by dehydration (freeze-drying) and rehydration followed by freeze-thaw sonication. Plain liposomes (N-liposomes) were prepared by the same process but without AF. HepG2 cells were incubated for 3 hours with free 3H-inulin, N-liposomal 3H-inulin, AF-liposomal 3H-inulin, or free AF. The cellular uptake of 3H-inulin and the cell viability were then determined. Uptake of AF-liposomes in a non-hepatoma cell line, NIH3T3, was also studied for comparison.

RESULTS:

Cellular uptake of free inulin was negligible while uptake of liposomal inulin, either in N-liposomes or in AF-liposomes, was significant (p < 0.01). The uptake of AF-liposomal inulin was significantly higher than that of N-liposomal inulin in HepG2 cells but not in NIH3T3 cells. Free AF and blank AF-liposomes inhibited the HepG2 cell uptake of AF-liposomal inulin.

CONCLUSIONS:

These results indicate that AF-liposomes enhanced intracellular delivery of a membrane-impermeable hydrophilic drug into hepatoma cells by a receptor mechanism. AF-liposomes are a potential drug carrier for intracellular delivery of membrane-impermeable hydrophilic drugs to HepG2 cells.

• Authors: H Y Yu, J H Lin
• Journal: Journal of the Formosan Medical Association = Taiwan yi zhi (J Formos Med Assoc) Vol. 99 Issue 12 Pg. 936-41 (Dec 2000) ISSN: 0929-6646 [Print] Singapore
• PMID: 11155748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Asialoglycoproteins
• Drug Carriers
• Liposomes
• Inulin

Topics

• 3T3 Cells (metabolism)
• Animals
• Asialoglycoproteins
• Cell Membrane Permeability
• Drug Carriers
• Humans
• Inulin (administration & dosage, pharmacokinetics)
• Liposomes
• Liver Neoplasms, Experimental (metabolism)
• Mice
• Tumor Cells, Cultured