Pluronic P105 sensitizes cholesterol-free liposomes to ultrasound

In this study, the ability of Pluronic P105 to sensitize liposomes to permeabilization by 20 kHz ultrasound (US) was investigated. Liposomes composed of egg phosphatidylcholine (PC) showed up to a ten-fold enhancement in US permeabilization when treated with low (μM) concentrations of Pluronic, as measured by the rate of leakage of an entrapped fluorescent dye. However, when 50 mol% cholesterol was included in the liposome formulation, the Pluronic was unable to increase the US permeabilization. In the absence of Pluronic, cholesterol has almost no effect on ultrasound responsivity of liposomes; thus, cholesterol is able to "protect" liposomal membranes from Pluronic. Pluronic P105 was also incorporated into the liposomes during formation and extrusion, and these liposome-polymer complexes retained high ultrasound responsivity. Interestingly, the ultrasound responsivity of the Pluronic-liposome complex increased significantly with temperature. These studies may suggest mechanisms for observed anti-tumor activity of P105, and may also help in the design of controlled-release vehicles.