Laboratory of Drug and Gene Delivery Research, Faculty of Pharma-Science, Teikyo University, Tokyo, Japan.
Department of Mechanical Engineering, The University of Tokyo, Tokyo, Japan.
J Pharm Sci. 2020 Sep;109(9):2827-2835. doi: 10.1016/j.xphs.2020.06.008. Epub 2020 Jun 12.
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 non-focused 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.
超声（US）微泡联合聚焦超声（FUS）打开血脑屏障（BBB）并向脑实质递送药物的能力引起了广泛关注。FUS 可以将超声能量集中在有限的空间内，而非聚焦超声可以影响广泛的组织区域。非聚焦超声也有望用于向大脑和其他组织输送药物。我们之前开发了基于脂质的微泡（LBs），并证明非聚焦超声和 LBs 具有向肿瘤组织递送药物的潜力。在这项研究中，为了实现高效和安全的脑靶向药物递送，我们使用非聚焦超声和 LBs 评估了 BBB 开放的特性。我们的结果表明，LBs 可以诱导非聚焦超声引起的 BBB 开放。US 频率和强度影响 BBB 开放和脑损伤的效率，并且表明 LBs 的剂量也与 BBB 开放的效率有关。此外，非聚焦 US 和 LBs 的组合可以将 2000 kDa 的大分子递送到大脑，并且发现 BBB 开放的诱导是可逆的。这些结果表明，非聚焦超声和 LBs 的联合具有作为脑靶向药物递送系统的潜力。
