Trapping of dextran-coated colloids in liposomes by transient binding to aminophospholipid: preparation of ferrosomes.
A procedure is described that allows to increase the efficiency of the loading of liposomes with dextran-stabilized iron oxides (MION). The method produces a preparation of liposomes (REVs) with high iron oxide content as a result of transient binding of oxidized dextran with amino groups of aminophospholipids. Phosphatidylethanolamine (PE)-containing lipid mixtures (PC/DOPE/CH or SM/DOPE/CH, 9:2:9 molar ratio) in organic phase were combined with oxidized MION at pH 8. Liposomes then were obtained by reversed-phase evaporation. Liposomes, 263 +/- 89 nm in diameter, contained up to 11.8 mol Fe/mol phospholipid (encapsulation yield 49%). 10.2% of liposome-associated iron was dissociated from liposomes upon changing the pH to 4.5. When lipid compositions of extracts prepared from liposomes incubated at pH 4.5 and pH 8.0 were compared, an increase of relative PE-content in extracts of liposomes incubated at lowered pH was detected. This indicates a dissociation of imine bonds between aldehydes on the MION surface and PE. The accessibility of liposomal PE for acylation was demonstrated by modification with an activated ester of methoxy poly(ethylene glycol) succinate. Control liposomes, containing no aminophospholipid, or PE-containing liposomes obtained in the presence of non-oxidized MION, were 3.5-5-fold less effective for MION encapsulation and showed extensive aggregation.
Bogdanov
A A
AA
Nuclear Magnetic Resonance Center, Department of Radiology, Massachusetts General Hospital, Boston 02129.
Martin
C
C
Weissleder
R
R
Brady
T J
TJ
D003102:Colloids / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D005290:Ferric Compounds; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008280:Magnetics; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry
D003102:Colloids; D003911:Dextrans; D005290:Ferric Compounds; D008081:Liposomes; D010714:Phosphatidylethanolamines; C067317:ferrosome; C000499:ferric oxide