UNGA Johan, OMATA Daiki, ODA Yusuke, SUGII Mutsumi, URUGA Hitoshi, MUNAKATA Lisa, SHIMA Tadamitsu, SUZUKI Ryo, MARUYAMA Kazuo

Johan UNGA, Daiki OMATA, Yusuke ODA, Mutsumi SUGII, Hitoshi URUGA, Lisa MUNAKATA, Tadamitsu SHIMA, Ryo SUZUKI, Kazuo MARUYAMA

¹Faculty of Pharma Sciences, Teikyo University, ²JSPS Research Fellow

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【Purpose】
To develop novel lipid-stabilized bubble formulations for ultrasound（US）imaging and therapy, as well as evaluate how different lipid compositions and different gases affect bubble stability.
【Methods】
Lipid-stabilized bubbles were prepared by homogenization of a lipid dispersion in the presence of perfluoropropane（PFP）or perfluorobutane（PFB）gas. Different ratios of the phospholipids distearoylphosphatidylcholine（DSPC）and distearoylphosphatidylglycerol（DSPG）together with a fixed percentage（10 mol％）of PEGylated phospholipid（DSPE-PEG）were tested and evaluated. After homogenization bubbles were freeze-dried with sucrose as cryo-protectant so that a dry cake containing bubbles was formed. After freeze-drying the vials were re-filled with gas and sealed. Samples were reconstituted with water and bubbles were analyzed for size and stability at high dilution in degased water in vitro using US imaging.
【Results and discussion】
Bubble diameters were around 1μm on average and could be satisfactorily preserved by freeze-drying and then re-constituted by addition of water to the dry sample. Changes in the lipid composition had a big impact on the properties of the bubbles produced. A mixture of DSPC and DSPG in a 1:2 molar ratio in PFP bubbles proved most stable with half-life of 3.8 min in vitro compared to 0.28 and 0.56 min for bubbles containing either DSPC or DSPG, respectively. Change of gas from PFP to PFB further increased the bubble stability.
【Acknowledgement】
This work was supported by MEXT-Supported Program for the Strategic Research Foundation at Private Universities 2013-2017.