Characterization of Brain-Targeted Drug Delivery Enhanced by a Combination of Lipid-Based Microbubbles and Non-Focused Ultrasound
Characterization of Brain-Targeted Drug Delivery Enhanced by a Combination of Lipid-Based Microbubbles and Non-Focused Ultrasound
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DOI：
10.1016/j.xphs.2020.06.008
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发表时间：
2020-09-01
影响因子：
3.8
通讯作者：
Suzuki, Ryo
中科院分区：
文献类型：
--
作者：
Omata, Daiki;Hagiwara, Fumiko;Suzuki, Ryo
聚焦超声（FUS）与超声造影剂微泡的结合，由于其能够打开血脑屏障（BBB）并将药物递送到脑实质的能力而引起了人们的广泛关注。FUS可以将US能量集中在有限的空间中，而非聚焦US可以影响广泛的组织区域。非聚焦超声也有希望用于向大脑和其他组织递送药物。我们以前开发了基于脂质的微泡（LB），并证明了非聚焦US和LB具有向肿瘤组织递送药物的潜力。在这项研究中，为了实现有效和安全的脑靶向药物递送，我们评估了使用非聚焦US和LB的BBB开放的特征。我们的研究结果表明，LB可以诱导BBB开放与非聚焦超声。超声频率和强度影响血脑屏障开放效率和脑损伤程度，并显示LB剂量也与血脑屏障开放效率相关。此外，非聚焦US和LB的组合可以向脑递送2000 kDa的大分子，并且发现BBB开放的诱导是可逆的。这些结果表明，非聚焦US和LB的组合具有作为脑靶向药物递送系统的潜力。(C)2020年美国药学协会（R）。爱思唯尔公司出版All rights reserved.
The combination of focused ultrasound (FUS) and microbubbles, an ultrasound (US) contrast agent, has attracted much attention for its ability to open the blood brain barrier (BBB) and deliver drugs to the brain parenchyma. FUS can concentrate US energy in a restricted space, whereas non-focused US can affect a wide area of tissue. Non-focused US is also promising for drug delivery to the brain and other tissues. We have previously developed lipid-based microbubbles (LBs), and demonstrated that nonfocused US and LBs have potential for drug delivery to tumor tissues. In this study, to achieve efficient and safe brain-targeted drug delivery, we evaluated the characteristics of BBB opening using non-focused US and LBs. Our results indicated that LBs could induce BBB opening with non-focused US. US frequency and intensity affected the efficiency of BBB opening and brain damage, and showed that the dose of LBs was also related to the efficiency of BBB opening. Furthermore, the combination of non-focused US and LBs could deliver macromolecules at 2000 kDa to the brain, and the induction of BBB opening was found to be reversible. These results suggest that the combination of non-focused US and LBs has potential as a brain-targeted drug delivery system. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.