Peg-Containing Surfactants Enhance the Ultrasonic Permeabilizability of Liposomes

Abstract

The susceptibility of phosphatidylcholine liposomes to rupture by ultrasound was investigated. The liposomes were treated with (or had incorporated) a surface active dopant. The dopants studied here all contain polymers or oligomers of ethylene glycol as their hydrophilic “headgroup” component. All dopants strongly increased the ultrasonic permeabilizability of liposomes, as measured by the rate of release of a self-quenching fluorescent dye, at concentrations that caused no increase in permeability in the absence of ultrasound. The surface active dopants reached maximal effectiveness at about 1% of their critical micelle concentrations (CMCs). Using the roughly inverse relationship between CMC and membrane partition coefficient, we estimate that these maximally effective concentrations correspond approximately to the onset of headgroup contact among the surfactants in the membrane. Two surfactants, a PEG-lipid and a Pluronic triblock polymer, can be irreversibly incorporated into liposomes to give formulations that could in principle be used as drug delivery vehicles. The Pluronic polymer offers the possibility of additional temperature responsivity, owing to its highly temperaturedependent CMC.