Effects of the liposomal formulation on the behavior and physical characteristics of acoustic liposomes

Ultrasound contrast agents (UCAs) are nano/microbubbles that contain air or a highmolecular-weight, low-solubility gas encapsulated in a lipid or albumin shell. Previous studies have developed acoustic liposomes (ALs), liposomes that encapsulate perfluoropropane (C₃F₈) gas. These ALs can be used as just UCAs, for early diagnostic or observation of angiogenesis. They can alsobe used for drug delivery, through their ultrasound-induced destruction leading to permeabilization of the neighboring cells. However, the echogenicity of ALs decreases within minutes, raising the need for more stable preparations. Here we show that the in vitro stability of ALs is affected by fluiditychanges in the bilayer, the presence of anionic phospholipids and the density of the PEG coating layer. These results allowed the preparation of "optimized" ALs displaying a 50% enhanced detection time in vitro. We anticipate their stability to be enhanced in a similar manner, in vivo. Further researchaims at further improvement of the stability of gas encapsulation by surface modification and coatingof the liposomes, and in vivo characterization of the optimized ALs.