In vitro characterization of liposomes and Optison by acoustic scattering at 3.5 MHz

Abstract

Objective: To assess the potential of immunoliposomes as an ultrasound contrast agent relative to albumen-stabilized microbubbles, a quantitative assessment of echogenicity was performed. Methods: Liposomes are stabilized phospholipid vesicles, which can encapsulate both gas and fluid. With antibody conjugation, this new formulation of immunoliposomes can be targeted to atheroma and other pathologic components, and thus they are being developed as novel diagnostic ultrasound echo contrast agents to enhance imaging of atherosclerosis. The diameter of the liposomes ranges from 0.25 to 5.0 microns. To measure the backscattering coefficient of liposome suspensions of varying concentrations, the backscattered power at 3.5 MHz was compared to that reflected from a planar air-water interface. The backscattering coefficient was also estimated theoretically as a function of air volume fraction by modeling the encapsulated air as a free air bubble and assuming single bubble scattering. Results: For most of the concentrations of liposomes used (on the order 108/ml), the backscattering coefficient equals or exceeds that of Optison (Mallinckrodt, Inc.) at the human clinical dose concentration (104/ml). The backscattering coefficient at 3.5 MHz appears to be a linear function of liposome concentration, suggesting that single bubble acoustic scattering theory holds. Conclusions: This detection technique shows promise as a sensitive method for determining whether the immunoliposomes are left intact or if they are destroyed during imaging, thus helping to explore their potential as a vehicle for targeted drug delivery.