Intracellular delivery of drugs by liposomes containing P0 glycoprotein from peripheral nerve myelin into human M21 melanoma cells.
The effect of P0 protein (a cell adhesion molecule from avian peripheral nerve myelin) on the rate of interaction of liposomes with human M21 melanoma cells was investigated. Liposome uptake by the cells was quantitated using radioactive lipids and liposome-entrapped drugs under various conditions. Liposomes containing P0 protein and [14C]dipalmitoylphosphatidylcholine:cholesterol (10:1 molar ratio) had an interaction rate with M21 cells three times higher than control vesicles of the same lipid composition but without the protein after incubation at 37 or 4 degrees C. The presence of P0 protein could be detected on the surface of melanoma cells by immunofluorescence after incubation. Binding to the cell surface and endocytosis of P0 liposomes was suggested from the sensitivity of cell-associated proteoliposomes to trypsin, metabolic inhibitors, and low temperature. Liposomal encapsulation highly increased the association of model compounds [( 3H]methotrexate and [3H]inulin) with cells. The proteoliposomes appeared to be leaky in the incubation medium, which led to the delivery of a lower amount of drug into cells than could be expected from their initial drug content. The results suggest that the attachment of liposomes to the cell surface can increase their drug delivery potential, because the binding triggers endocytic processes or a juxtapositional temporary permeability increase of liposome and cellular membrane that can lead to the uptake of drug from liposomes.
Foldvari
M
M
College of Pharmacy, Dalhousie University, Halifax, Nova Scotia, Canada.
Mezei
C
C
Mezei
M
M
D015816:Cell Adhesion Molecules, Neuronal; D003911:Dextrans / Q000008:administration & dosage; D004337:Drug Carriers; D005455:Fluorescent Antibody Technique; D005492:Folic Acid; D006801:Humans; D007444:Inulin / Q000008:administration & dosage; D050356:Lipid Metabolism; D008081:Liposomes; D008545:Melanoma / Q000378:metabolism*; D008727:Methotrexate / Q000008:administration & dosage; D008856:Microscopy, Fluorescence; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000737:chemistry*; D010525:Peripheral Nerves / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D015816:Cell Adhesion Molecules, Neuronal; D003911:Dextrans; D004337:Drug Carriers; D008081:Liposomes; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D007444:Inulin; D005492:Folic Acid; D008727:Methotrexate