Brain Delivery of Curcumin Through Low-Intensity Ultrasound-Induced Blood-Brain Barrier Opening via Lipid-PLGA Nanobubbles.
Brain Delivery of Curcumin Through Low-Intensity Ultrasound-Induced Blood-Brain Barrier Opening via Lipid-PLGA Nanobubbles.
复制标题
通过脂质-PLGA 纳米气泡低强度超声诱导血脑屏障开放向大脑输送姜黄素
DOI：
10.2147/ijn.s327737
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发表时间：
2021
影响因子：
8
通讯作者：
Yan F
中科院分区：
文献类型：
--
作者：
Yan Y;Chen Y;Liu Z;Cai F;Niu W;Song L;Liang H;Su Z;Yu B;Yan F
帕金森病(PD)是一种进行性神经退行性疾病。由于血脑屏障(BBB)的存在，传统的药物很难作用于病变的细胞核，并发挥其抑制或延缓PD进展的作用。最近的文献表明，姜黄素在治疗帕金森病方面显示出巨大的潜力。然而，由于其药效性差，通过BBB的生物利用度低，在体内的应用仍然困难。采用熔融结晶法改善姜黄素的溶解性，将姜黄素包裹到脂质-PLGA纳米泡囊中，制备了姜黄素脂质-PLGA纳米泡囊(CuR-NBS)。用一系列分析方法对Cur-NBS的气泡大小、Zeta电位、超声成像能力和药物包封率进行了表征。采用低强度聚焦超声(LIFU)结合Cur-NB打开血脑屏障，促进姜黄素进入PD小鼠脑内，并对其治疗效果进行行为学评价。熔融结晶法提高了姜黄素的溶解度，是纯姜黄素的2627倍。得到的CuR-NBS具有约400 nm的纳米尺寸，并显示出优异的对比度成像性能。在最佳声压下照射Cur-NBS可有效释放包裹在Cur-NBS中的姜黄素药物，在6h内可达到30%的累积释放率。重要的是，Cur-NBS联合Lifu能开放血脑屏障并将姜黄素局部输送到脑深部核团，与单独使用Cur-NBS和Lifu组相比，显著增强了姜黄素对帕金森C57BL/6J小鼠模型的疗效。在本工作中，我们极大地改善了姜黄素的溶解性，并通过与利福平介导的血脑屏障相结合，开发了姜黄素抗帕金森病脑内递送的Cur-NBS。CUR-NBS为这些难以跨越血脑屏障治疗帕金森病或其他中枢神经系统(CNS)疾病的潜在药物提供了一个平台。
Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Owing to the presence of blood–brain barrier (BBB), conventional pharmaceutical agents are difficult to the diseased nuclei and exert their action to inhibit or delay the progress of PD. Recent literatures have demonstrated that curcumin shows the great potential to treat PD. However, its applications are still difficult in vivo due to its poor druggability and low bioavailability through the BBB. Melt-crystallization methods were used to improve the solubility of curcumin, and curcumin-loaded lipid-PLGA nanobubbles (Cur-NBs) were fabricated through encapsulating the curcumin into the cavity of lipid-PLGA nanobubbles. The bubble size, zeta potentials, ultrasound imaging capability and drug encapsulation efficiency of the Cur-NBs were characterized by a series of analytical methods. Low-intensity focused ultrasound (LIFU) combined with Cur-NB was used to open the BBB to facilitate curcumin delivery into the deep brain of PD mice, followed by behavioral evaluation for the treatment efficacy. The solubility of curcumin was improved by melt-crystallization methods, with 2627-fold higher than pure curcumin. The resulting Cur-NBs have a nanoscale size about 400 nm and show excellent contrast imaging performance. Curcumin drugs encapsulated into Cur-NBs could be effectively released when Cur-NBs were irradiated by LIFU at the optimized acoustic pressure, achieving 30% cumulative release rate within 6 h. Importantly, Cur-NBs combined with LIFU can open the BBB and locally deliver the curcumin into the deep-seated brain nuclei, significantly enhancing efficacy of curcumin in the Parkinson C57BL/6J mice model in comparison with only Cur-NBs and LIFU groups. In this work, we greatly improved the solubility of curcumin and developed Cur-NBs for brain delivery of curcumin against PD through combining with LIFU-mediating BBB. Cur-NBs provide a platform for these potential drugs which are difficult to cross the BBB to treat PD disease or other central nervous system (CNS) diseases.