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 (mPEG 2000 ‐DSPE) could be transferred into preformed, drug‐containing liposomes from the micelles in a temperature‐ and time‐dependent manner. Antibody densities up to 100 μg antibody/μmol of phospholipid, and up to 3 mol% of mPEG 2000 ‐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.