Preparation and characterization of microbubbles for ultrasoundimaging

Abstract

Ultrasound is widely used in clinical settings for diagnosis of diseases. However, the image quality in some cases is not at desirable level because most of the tissues have similar acoustic properties to many tumors. Microbubbles administired to the systemic circulation during imaging are known to increase the quality, creating contrast with respect to the surrounding tissues. Unfortunately, current formulations of microbubbles composed of phospholipid (mainly PC) and emulsifier have been found to be unstable for ultrasound imaging. In this study, it was aimed to engineer the shell structure of microbubbles to develop more stable, targetable microbubbles and investigate their adhesion characteristics to breast cancer cells as a model system. Our results indicated that increasing content of PEG40 St in the formulation resulted in microbubbles with higher yield and stability, being optimum at 50 mole %. Incorporation of lipopolymers as emulsifier instead of PEG40St in the formulation influenced stability adversely. Addition of a phospholipid capable of secondary interactions to the formulation had improved stability and size of the microbbubles, depending on the content and type of head group of the phospholipid. Usage of less water-soluble gas in the core of new microbubbles did not have further effect on the stability, as observed with the microbubbles of the current formulation. This result may suggest that the new microbubbles’ shell is densely packed such that gas diffusion is enormously minimized/inhibited. Moreover, selected formulations developed in this study provided much more adhesion than the current formulation to the cell of interest.