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Expert Opin Drug Deliv. 2014 May;11(5):711-21. doi: 10.1517/17425247.2014.897693. Epub 2014 Mar 20.
The presence of the blood-brain barrier (BBB) is a significant impediment to the delivery of therapeutic agents to the brain for treatment of brain diseases. Focused ultrasound (FUS) has been developed as a noninvasive method for transiently increasing the permeability of the BBB to promote drug delivery to targeted regions of the brain.
The present review briefly compares the methods used to promote drug delivery to the brain and describes the benefits and limitations of FUS technology. We summarize the experimental data which shows that FUS, combined with intravascular microbubbles, increases therapeutic agent delivery into the brain leading to significant reductions in pathology in preclinical models of disease. The potential for translation of this technology to the clinic is also discussed.
The introduction of magnetic resonance imaging guidance and intravascular administration of microbubbles to FUS treatments permits the consistent, transient and targeted opening of the BBB. The development of feedback systems and real-time monitoring techniques improve the safety of BBB opening. Successful clinical translation of FUS has the potential to revolutionize the treatment of brain disease resulting in effective, less-invasive treatments without the need for expensive drug development.
血脑屏障(BBB)的存在是将治疗药物递送到大脑以治疗脑部疾病的重大障碍。聚焦超声(FUS)已被开发为一种非侵入性方法,可短暂增加 BBB 的通透性,以促进药物递送到大脑的靶向区域。
本综述简要比较了用于促进药物递送到大脑的方法,并描述了 FUS 技术的优势和局限性。我们总结了实验数据,表明 FUS 联合血管内微泡可增加治疗剂向大脑的递送,从而导致疾病的临床前模型中的病理显著减少。还讨论了将这项技术转化为临床应用的潜力。
将磁共振成像引导和血管内微泡给药引入 FUS 治疗中,可以实现 BBB 的一致、短暂和靶向开放。反馈系统和实时监测技术的发展提高了 BBB 开放的安全性。FUS 的成功临床转化有可能彻底改变脑部疾病的治疗方法,实现有效、微创的治疗,而无需昂贵的药物开发。