TECHNIQUE FOR THE CHARACTERIZATION OF PHOSPHOLIPID MICROBUBBLES COATINGS BY TRANSMISSION ELECTRON MICROSCOPY

Gas microbubbles stabilized by a surfactant or polymer coating are of considerable clinical interest because of their imaging and drug delivery potential under ultrasound exposure. The utility of microbubbles for a given application is intrinsically linked to their structure and stability. These in turn are highly sensitive to coating composition and fabrication techniques. Various methods including fluorescence and atomic force microscopy have been applied to characterizemicrobubble properties, but direct observation of coating structure at the nanoscale still poses a considerable challenge. Here we describe a transmission electronmicroscopy (TEM) technique to observe the surface of microbubbles. Images from a series of phospholipid-coated microbubble systems, including those decorated with nanoparticles, are presented. They indicate that the technique enables visualization of the coating structure, in particular lipid discontinuities and nanoparticle distribution. This information can be used to better understand how microbubble surface structure relates to formulation and/or processing technique and ultimately to functionality. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology.