Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Health Technology, Technical University Denmark, Kongens Lyngby, Denmark.
Ultrasound Med Biol. 2021 May;47(5):1343-1355. doi: 10.1016/j.ultrasmedbio.2021.01.014. Epub 2021 Feb 16.
The blood-brain barrier (BBB) is a major obstacle to treating several brain disorders. Focused ultrasound (FUS) in combination with intravascular microbubbles increases BBB permeability by opening tight junctions, creating endothelial cell openings, improving endocytosis and increasing transcytosis. Here we investigated whether combining FUS and microbubbles with transferrin receptor-targeting liposomes would result in enhanced delivery to the brain of post-natal rats compared with liposomes lacking the BBB-targeting moiety. For all animals, increased BBB permeability was observed after FUS treatment. A 40% increase in accumulation of transferrin receptor-targeting liposomes was observed in the FUS-treated hemisphere, whereas the isotype immunoglobulin G liposomes showed no increased accumulation. Confocal laser scanning microscopy of brain sections revealed that both types of liposomes were mainly observed in endothelial cells in the FUS-treated hemisphere. The results demonstrate that FUS and microbubble treatment combined with BBB-targeting liposomes could be a promising approach to enhance drug delivery to the brain.
血脑屏障（BBB）是治疗几种脑部疾病的主要障碍。聚焦超声（FUS）与血管内微泡联合使用，通过打开紧密连接、形成内皮细胞开口、促进内吞作用和增加转胞吞作用来增加 BBB 的通透性。在这里，我们研究了 FUS 和微泡与转铁蛋白受体靶向脂质体联合使用是否会导致新生大鼠脑内的递药增强，与缺乏 BBB 靶向部分的脂质体相比。对于所有动物，FUS 治疗后均观察到 BBB 通透性增加。在 FUS 治疗的半球中，观察到转铁蛋白受体靶向脂质体的积累增加了 40%，而同种型免疫球蛋白 G 脂质体则没有增加的积累。脑切片的共聚焦激光扫描显微镜显示，两种类型的脂质体主要在 FUS 治疗的半球中的内皮细胞中观察到。结果表明，FUS 和微泡联合应用与 BBB 靶向脂质体联合应用可能是增强药物向脑内递药的一种有前途的方法。
