A morphologic and biochemical study of the fate of antibody-bearing liposomes.
The effect of the intravenous administration of gamma-globulins, entrapped or not within liposomes, was investigated in rodent liver. Desialation of gamma-globulins did not influence significantly their uptake by this organ. Fluorescein-labeled nonspecific gamma-globulins and antibodies raised against the lysosomal acid alpha-glucosidase were entrapped within two types of liposomes. The administration of negatively charged liposomes made of lecithin, cholesterol, and dicetylphosphate was badly tolerated. Positively charged liposomes, in which dicetylphosphate was replaced by stearylamine, allowed a considerably higher yield of entrapment and were well tolerated by the animals. Approximately half of the fluorescent gamma-globulins were recovered in the liver, and evidence is presented for the intralysosomal localization of positively charged liposomes, both in the reticuloendothelial cells and in the hepatocytes. A striking difference exists, nevertheless, in the appearance of the two types of cells, 1 hour and 7 1/2 hours after injection. The specific antibodies never inhibited more than 50% of the activity of liver acid alpha-glucosidase, and there was no significant modification in the glycogen content of this organ. This work points to the influence of the composition of liposomes, in determining the entrapment of proteins, the toxicity, the uptake by the liver, and the distribution of these lipidic spherules in the different types of cells. This factor will have to be taken into account if liposomes are to be used as vectors in the treatment of lysosomal storage diseases.
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D000917:Antibody Formation; D005260:Female; D005959:Glucosidases / Q000276:immunology / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism*; D008099:Liver / Q000032:analysis / Q000648:ultrastructure*; D008112:Liver Glycogen / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology* / Q000648:ultrastructure; D051379:Mice; D051381:Rats; D005719:gamma-Globulins / Q000008:administration & dosage / Q000032:analysis
D000906:Antibodies; D008081:Liposomes; D008112:Liver Glycogen; D005719:gamma-Globulins; D005959:Glucosidases