Synthesis of echogenic liposomes for sonoporation

Abstract

Ultrasound contrast agents (UCAs), which are groups of engineered microbubbles, have been recently studied for drug delivery applications, since the cavitation of bubbles can increase the temporary permeability of nearby cells. However, the internal volume of UCAs is generally filled with gas, hence loading drug molecules into UCAs is limited. In this study, an echogenic liposome with a liquid and gas core is proposed as an alternative carrier of genetic material for ultrasound-mediated drug delivery. The structure of the synthesized echogenic liposome was analysed via transmission electron microscopy and confocal microscopy with fluorescent labels. The protection of siRNA by the echogenic liposomes was also verified by exposure to RNase. The results indicate that at least 10% of the total siRNA used in the experiment was successfully protected by the proposed echogenic liposome. Additionally, the release of siRNA from the liposomes could be successfully achieved with 1 W/cm2 ultrasound sonication at 1 MHz; parameters low enough to be used in generic ultrasound therapeutic systems. Although further studies to clarify the responses to incident ultrasound fields and to quantitatively analyse the internal liquid volume for drug loading are required, the proposed echogenic liposome has great potential for ultrasound-mediated gene delivery.