Preparation of asialofetuin-labeled liposomes with encapsulated human interferon-gamma and their uptake by isolated rat hepatocytes.
The selective delivery of human recombinant interferon (IFN)-gamma to isolated rat hepatocytes was studied with asialofetuin (AF)-labeled liposomes. AF-liposomes containing buffer solution were initially prepared by the detergent removal method, and IFN-gamma was subsequently encapsulated by the freeze-thawing method without loss of activity. Virtually no free [32P]IFN-gamma was internalized into isolated rat hepatocytes, whereas AF-liposomes containing [32P]IFN-gamma were taken up to a significant degree. Liposomal binding to the hepatocytes (estimated at 4 degrees C) was one-fifth of the uptake (estimated at 37 degrees C). Since the uptake was inhibited by the addition of free AF, AF-liposomes may be taken up by the action of galactose-binding protein on the hepatocytic cell surface. The liposome preparation method reported in this paper provides a useful means for the encapsulation of unstable macromolecules into AF-liposomes. AF-liposomes were found effectively to carry IFN-gamma into hepatocytes in vitro.
Tokyo College of Pharmacy, Japan.
H
H
Ishihara
T
T
Hara
Y
Y
Aramaki
S
S
Tsuchiya
K
K
Hosoi
D000818:Animals; D001212:Asialoglycoproteins; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003902:Detergents; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D060748:Fetuins; D005615:Freezing; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008081:Liposomes; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D011863:Radioimmunoassay; D051381:Rats; D000509:alpha-Fetoproteins
D001212:Asialoglycoproteins; D003902:Detergents; D004337:Drug Carriers; D060748:Fetuins; D008081:Liposomes; D010761:Phosphorus Radioisotopes; D000509:alpha-Fetoproteins; C017029:asialofetuin; D007371:Interferon-gamma