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A combinatorial approach to producing sterically stabilized (Stealth) immunoliposomal drugs
Author(s) -
Ishida Tatsuhiro,
Iden Debbie L,
Allen Theresa M
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01320-4
Subject(s) - liposome , micelle , chemistry , polyethylene glycol , peg ratio , steric effects , biophysics , phospholipid , ligand (biochemistry) , combinatorial chemistry , vesicle , drug , ethylene glycol , chromatography , biochemistry , stereochemistry , membrane , organic chemistry , pharmacology , receptor , biology , finance , aqueous solution , economics
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.