Novel Immunoliposomes Modified with Amphipathic Polyethyleneglycols Conjugated at their Distal Terminals to Monoclonal Antibodies
Distearoyl-N-(3-carboxypropionoyl polyethyleneglycol succinyl) phosphatidylethanolamine (DSPE-PEG-COOH) was newly synthesized and used to prepare novel immunoliposomes carrying monoclonal antibodies at the distal ends of the PEG chains (Type C). Liposomes were prepared from egg phosphatidylcholine (ePC) and cholesterol (CH) (2:1, m/m) containing 6 mol% of DSPE-PEG-COOH, and a monoclonal IgG antibody, 34A, which is highly specific to pulmonary endothelial cells, was conjugated to the carboxyl groups of DSPE-PEG-COOH to give various amounts of antibody molecules per liposome. Type C liposomes without antibodies showed prolonged circulation time and reduced reticuloendothelial system (RES) uptake owing to the presence of PEG. The degree of lung binding of 34A-Type C was about 1.3-fold higher than that of 34A-conventional immunoliposomes (34A-Type A), indicating that recognition by the antibodies attached to the PEG terminal was not sterically hindered and that the free PEG (i.e., that not carrying antibody) was effective in increasing the blood concentration of immunoliposomes by enabling them to evade RES uptake. Our approach provides a simple means of conjugating antibodies directly to the distal end of PEG which is already bound to the liposome membrane, and should contribute to the development of superior targetable drug delivery vehicles for use in diagnostics and therapy.
KeywordsReticuloendothelial System Target Binding Antibody Molecule Liposome Membrane Simple Means
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