A combinatorial approach to producing sterically stabilized (Stealth) immunoliposomal drugs.
We have developed a method for producing sterically stabilized immunoliposomal drugs (SIL) readily applicable to a 'mix and match' combinatorial approach for the simple manufacture of a variety of ligand-targeted liposomal drugs. Ligands coupled to the terminus of polyethylene glycol (PEG) in micelles formed from PEG-lipid derivatives (mPEG2000-DSPE) could be transferred into preformed, drug-containing liposomes from the micelles in a temperature- and time-dependent manner. Antibody densities up to 100 microg antibody/micromol of phospholipid, and up to 3 mol% of mPEG2000-DSPE, could be simultaneously transferred from the ligand-coupled micelles into the liposomal outer monolayer with negligible drug leakage from liposomes during transfer and good stability in human plasma. Transfer of anti-CD19 into SIL resulted in a three-fold increase in binding of these liposomes to CD19+ human B cell lymphoma cells.
Ishida
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Department of Pharmacology, University of Alberta, Edmonton, Canada.
Iden
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Allen
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D000906:Antibodies / Q000737:chemistry* / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology; D000970:Antineoplastic Agents / Q000737:chemistry; D002499:Centrifugation, Density Gradient; D020650:Combinatorial Chemistry Techniques; D004317:Doxorubicin / Q000737:chemistry; D004337:Drug Carriers; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry* / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology; D008823:Micelles; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000906:Antibodies; D018941:Antigens, CD19; D000970:Antineoplastic Agents; D004337:Drug Carriers; D007074:Immunoglobulin G; D008081:Liposomes; D008823:Micelles; D010714:Phosphatidylethanolamines; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D004317:Doxorubicin