Shuttle-Mediated Nanoparticle Transport Across an In Vitro Brain Endothelium Under Flow Conditions
Shuttle-Mediated Nanoparticle Transport Across an In Vitro Brain Endothelium Under Flow Conditions
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DOI：
10.1002/bit.26221
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发表时间：
2017-05-01
影响因子：
3.8
通讯作者：
Netti, Paolo A.
中科院分区：
文献类型：
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作者：
Falanga, Andrea P.;Pitingolo, Gabriele;Netti, Paolo A.
血脑屏障（BBB）代表了开发能够到达中枢神经系统（CNS）的新纳米递送系统的挑战。为了测试这些纳米载体的功效，使用类似于体内细胞培养条件的体外模型是至关重要的。在这里，我们首次证明了亲膜肽（即gH 625）在模拟血液流速的流动条件下运输货物（充当穿梭机）穿过BBB层的能力。为此，BBB微流控装置设计的基础上，一个透明的聚酯多孔膜夹在顶部和底部覆盖通道由聚（甲基丙烯酸甲酯）（PMMA）。我们的数据清楚地表明，这种微流体系统允许脑内皮细胞弯曲的生长。3个细胞，并在培养7天时形成汇合层，与单独的多孔膜相比，汇合层阻碍了纳米颗粒的通过。该装置在5 μ L/min的工作流速下进行验证，其中显示了模型在纳米颗粒通过后保持完整的能力。非常有趣的是，用gH 625肽装饰增强了纳米颗粒与内皮层的粘附和流动条件下的BBB交叉，从而证实了gH 625作为脑递送平台的功效。(C)2016 Wiley Periodicals，Inc.
The blood brain barrier (BBB) represents a challenge in the development of new nano-delivery systems able to reach the central nervous system (CNS). In order to test the efficacy of these nanocarriers, it is fundamental to use in vitro models that resemble the in vivo cell culture conditions. Here, we demonstrate for the first time the ability of a membranotropic peptide, namely gH625, to transport a cargo-acting as a shuttle-across the BBB layer under flow conditions that mimic the blood flow rate. To this aim, a BBB microfluidic device was designed based on a transparent polyester porous membrane sandwiched between a top and a bottom overlying channel made of poly(methyl methacrylate) (PMMA). Our data clearly indicate that this microfluidic system allows the growth of brain endothelial bEnd. 3 cells and the formation of a confluent layer at 7 days of culture that hinders the passage of nanoparticles compared to porous membrane alone. The device was validated at a 5 mu L/min working flow rate, where the capability of the model to remain intact after nanoparticle passage was shown. Very interestingly, the decoration with the gH625 peptide enhances the adhesion of nanoparticles to the endothelial layer and the BBB crossing in flow conditions, thus confirming the efficacy of the gH625 as a delivery platform to the brain. (C) 2016 Wiley Periodicals, Inc.