Effects of encapsulated gas on stability of lipid-based microbubbles and ultrasound-triggered drug delivery
2019
Abstract The combination of Ultrasound (US) and US contrast agent (
microbubbles, MBs), which is gas stabilized by a shell such as phospholipids or proteins, has potential as a useful innovative diagnostic and therapeutic tool. Previous studies have evaluated how particle size or shell components of MBs affect their physical characteristics, imaging ability, and
drug deliveryefficacy. We reported that MBs composed of neutral, anionic phospholipids, and polyethylene glycol-conjugated phospholipids at appropriate ratios were highly stable for US imaging. However, the effects of encapsulated gas on stability and
drug deliveryefficacy have not been characterized. Therefore, we developed several gas-loaded MBs with identical shell compositions and assessed their stability by US imaging (LOGIQ E9 with ML6-15 probe, MI 0.20). In addition, we assessed the effects of gas encapsulated in MBs on brain-
targeted drug delivery, because the
brainrequires an efficient
drug deliverysystem. Perfluoropropane and
perfluorobutane-loaded MBs (MB-C3F8 and MB-C4F10) showed sustained US imaging in vitro and in vivo compared with
sulfur hexafluoride-loaded MBs (MB-SF6). In addition, treatment of MB-C3F8 and MB-C4F10 with non-focused US efficiently delivered
Evans blue, which was used as a model drug, to the brain to a greater extent than MB-SF6. In these treatments, notable damage to brain was not observed, which was assessed by HE staining and denatured neuron staining. Our results suggested that perfluoropropane and
perfluorobutanecould be useful for the production of MBs with high stability to allow for US imaging and
drug delivery.
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