Shell properties and concentration stability of acoustofluidic delivery agents.

This paper investigates the shell elastic properties and the number-concentration stability of a new acoustofluidic delivery agent liposome in comparison to Definity™, a monolayer ultrasonic contrast agent microbubble. The frequency dependent attenuation of an acoustic beam passing through a microbubble suspension was measured to estimate the shell parameters. The excitation voltage was adjusted to ensure constant acoustic pressure at all frequencies. The pressure was kept at the lowest possible magnitude to ensure that effects from nonlinear bubble behaviour which are not considered in the analytical model were minimal. The acoustofluidic delivery agent shell stiffness Sp and friction Sf parameters were determined as (Sp = 0.11 N/m, Sf = 0.31 × 10-6 Kg/s at 25 °C) in comparison to the Definity™ monolayer ultrasound contrast agent which were (Sp = 1.53 N/m, Sf = 1.51 × 10-6 Kg/s at 25 °C). When the temperature was raised to physiological levels, the friction coefficient Sf decreased by 28% for the monolayer microbubbles and by only 9% for the liposomes. The stiffness parameter Sp of the monolayer microbubble decreased by 23% while the stiffness parameter of the liposome increased by a similar margin (27%) when the temperature was raised to 37 °C. The size distribution of the bubbles was measured using Tunable Resistive Pulse Sensing (TRPS) for freshly prepared microbubbles and for bubble solutions at 6 h and 24 h after activation to investigate their number-concentration stability profile. The liposome maintained >80% of their number-concentration for 24 h at physiological temperature, while the monolayer microbubbles maintained only 27% of their number-concentration over the same period. These results are important input parameters for the design of effective acoustofluidic delivery systems using the new liposomes.