Nanoparticle delivery to the brain - By focused ultrasound and self-assembled nanoparticle-stabilized microbubbles
Nanoparticle delivery to the brain - By focused ultrasound and self-assembled nanoparticle-stabilized microbubbles
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DOI：
10.1016/j.jconrel.2015.10.047
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发表时间：
2015-12-28
影响因子：
10.8
通讯作者：
Davies, Catharina de Lange
中科院分区：
文献类型：
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作者：
Aslund, Andreas K. O.;Berg, Sigrid;Davies, Catharina de Lange
血脑屏障（BBB）是药物进入中枢神经系统（CNS）的重要屏障。纳米颗粒已经能够部分克服这一障碍，因此可以改善药物通过血脑屏障的递送。此外，在动物模型中，聚焦超声结合充气微泡以时空方式打开BBB，从而促进药物递送穿过BBB。在目前的研究中，我们联合收割机这两种方法在我们的追求，开发一种新的，通用的方法，通过血脑屏障和中枢神经系统的药物输送。使用聚合物聚（氰基丙烯酸丁酯）（PBCA）合成纳米颗粒，并且已报道此类纳米颗粒在一定程度上穿过BBB。与蛋白质一起，这些纳米颗粒自组装成微泡。使用这些新型微泡与聚焦超声相结合，我们成功且安全地短暂打开了健康大鼠的血脑屏障。此外，我们还证明了纳米颗粒可以穿过血脑屏障并将模型药物递送到CNS中。(C)2015爱思唯尔B.V.保留所有权利。
The blood-brain barrier (BBB) constitutes a significant obstacle for the delivery of drugs into the central nervous system(CNS). Nanoparticles have been able to partly overcome this obstacle and can thus improve drug delivery across the BBB. Furthermore, focused ultrasound in combination with gas filled microbubbles has opened the BBB in a temporospatial manner in animal models, thus facilitating drug delivery across the BBB. In the current study we combine these two approaches in our quest to develop a novel, generic method for drug delivery across the BBB and into the CNS. Nanoparticles were synthesized using the polymer poly(butyl cyanoacrylate) (PBCA), and such nanoparticles have been reported to cross the BBB to some extent. Together with proteins, these nanoparticles self-assemble into microbubbles. Using these novel microbubbles in combination with focused ultrasound, we successfully and safely opened the BBB transiently in healthy rats. Furthermore, we also demonstrated that the nanoparticles could cross the BBB and deliver a model drug into the CNS. (C) 2015 Elsevier B.V. All rights reserved.