Polymeric nano/microcapsules of liquid perfluorocarbons for ultrasonic imaging: physical characterization

Ultrasonic imaging is a widely available, noninvasive, and cost-effective diagnostic modality, but vessels smaller than 200 mum in diameter are impossible to visualize. Commercial ultrasound contrast agents (UCAs), consisting of encapsulated gas microbubbles injected intravenously, enable only a qualitative visualization of the microvascularization for a short period of time since they are rather unstable. In a strategy to develop more stable UCAs, we designed a process to obtain nano/microcapsules with a single core of liquid perfluorocarbons within a biodegradable polymeric shell of homogeneous thickness. The polymer shell should improve the stability of the capsules as compared to UCAs stabilized by a monomolecular layer, while the acoustic impedance of the perfluorocarbons should ensure their echogenicity. These capsules have been optimized to encapsulate several liquid perfluorocarbons: perfluorohexane, perfluorodecalin, and perfluorooctyl bromide. The system is rather versatile: the mean size of the capsules can be adjusted between 70 nm and 25 microm and the thickness-to-radius ratio (T/R) can be easily modulated by simply modifying the polymer-to-perfluorocarbon ratio. T/R does not depend on the size of the capsules and is between 0.2 and 0.6. The dependence of the echogenic properties of the capsules with their size and their T/R has yet to be studied experimentally before this system can be evaluated in vivo.