Development and evaluation of stability and ultrasound response of DSPC-DPSG-based freeze-dried microbubbles

AbstractIt is known that Phosphatidyl choline-Phosphatidyl glycerol mixtures can be used for liposome formulations, making them less leaky than liposomes with only one lipid. We hypothesized that this might also be the case for bubbles, which can be used as ultrasound (US) contrast agents. Therefore, we have compared a series of mixed distearoyl phosphatidylcholine-distearoyl phosphatidylglycerol (DSPC-DPSG) bubbles and with bubbles containing either DSPC or DSPG (and distearoyl ethanolamine-polyethyleneglycol 2000, DSPE-PEG2k). Here, we describe the development, examination of stability in vitro and attenuation of broad frequency US pulses.Novel lipid stabilized freeze-dried formulations for ultrasound (US) applications, using the phospholipids DSPC, DSPG, and PEGylated DSPE-PEG2k and perfluorpropane gas, were developed. It was found that the bubbles could effectively be preserved by freeze-drying and then re-constituted by addition of water. Average bubble sizes were around 2 µm for all bubbles after re...