Langmuir, Vol.19, No.14, 5608-5617, 2003
Combined cryogenic transmission electron microscopy and electron spin resonance studies of egg phosphatidylcholine liposomes loaded with a carboranyl compound intended for boron neutron capture therapy
The lactosyl carborane [1,2-dicarba-closo-dodecarboran(12)-1-ylmethyl](beta-D-galactopyranosyl)-(1-->4)-beta-gluco-pyranoside (LCOB) is an amphipilic boron-containing compound intended for boron neutron capture therapy. In this study cryogenic transmission electron microscopy was used to investigate the effects of LCOB on the structure and properties of extruded egg phosphatidylcholine liposomes. The results showed that LCOB concentrations up to at least x(LCOB) = 0.25 could be included in the preparations without any noticeable effects on the liposomal size or structure. Inclusion of LCOB concentrations corresponding to x(LCOB) = 0.44 or more gave, however, rise to significant changes in the liposome size distribution and the overall sample structure. In fresh samples no signs of phospholipid solubilization were detected until the molar fraction of LCOB reached 0.82. At this concentration the boronated compound induced, however, formation of open liposomes and threadlike micelles and, furthermore, with time the sample displayed a macroscopic phase separation. More details on the molecular interaction between LCOB and the liposome membranes were obtained by electron spin resonance spectroscopy. Two different n-doxyl stearic acid spin probes were used to measure the dynamics and the degree of order in the mixed systems. The results indicated that LCOB insertion into the phospholipid bilayer increased the packing order in the vicinity of the water/hydrocarbon interface whereas the inner hydrophobic region of the bilayer was unaffected.