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Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery.
International Journal of Nanomedicine ( IF 8 ) Pub Date : 2020-06-11 , DOI: 10.2147/ijn.s247985
Alexander J Willis 1 , Sebastian P Pernal 2 , Zachary A Gaertner 3 , Sajani S Lakka 1 , Michael E Sabo 4 , Francis M Creighton 4 , Herbert H Engelhard 5
Affiliation  

Background: Magnetic nanoparticles (MNPs) hold promise for enhancing delivery of therapeutic agents, either through direct binding or by functioning as miniature propellers. Fluid-filled conduits and reservoirs within the body offer avenues for MNP-enhanced drug delivery. MNP clusters can be rotated and moved across surfaces at clinically relevant distances in response to a rotating magnet. Limited data are available regarding issues affecting MNP delivery by this mechanism, such as adhesion to a cellular wall. Research reported here was initiated to better understand the fundamental principles important for successful implementation of rotational magnetic drug targeting (rMDT).
Methods: Translational movements of four different iron oxide MNPs were tested, in response to rotation (3 Hz) of a neodymium–boron–iron permanent magnet. MNP clusters moved along biomimetic channels of a custom-made acrylic tray, by surface walking. The effects of different distances and cellular coatings on MNP velocity were analyzed using videography. Dyes (as drug surrogates) and the drug etoposide were transported by rotating MNPs along channels over a 10 cm distance.
Results: MNP translational velocities could be predicted from magnetic separation times. Changes in distance or orientation from the magnet produced alterations in MNP velocities. Mean velocities of the fastest MNPs over HeLa, U251, U87, and E297 cells were 0.24 ± 0.02, 0.26 ± 0.02, 0.28 ± 0.01, and 0.18 ± 0.03 cm/sec, respectively. U138 cells showed marked MNP adherence and an 87.1% velocity reduction at 5.5 cm along the channel. Dye delivery helped visualize the effects of MNPs as microdevices for drug delivery. Dye delivery by MNP clusters was 21.7 times faster than by diffusion. MNPs successfully accelerated etoposide delivery, with retention of chemotherapeutic effect.
Conclusion: The in vitro system described here facilitates side-by-side comparisons of drug delivery by rotating MNP clusters, on a human scale. Such microdevices have the potential for augmenting drug delivery in a variety of clinical settings, as proposed.



中文翻译:

旋转磁性纳米粒子簇作为药物输送的微型装置。

背景:磁性纳米粒子(MNPs)有望通过直接结合或通过充当微型螺旋桨来增强治疗剂的递送。体内充满液体的导管和储液罐为 MNP 增强的药物输送提供了途径。MNP 簇可以响应旋转磁体以临床相关距离在表面上旋转和移动。关于通过这种机制影响 MNP 递送的问题的数据有限,例如与细胞壁的粘附。此处报告的研究旨在更好地理解对成功实施旋转磁性药物靶向 (rMDT) 很重要的基本原则。
方法:测试了四种不同氧化铁 MNP 的平移运动,以响应钕-硼-铁永磁体的旋转 (3 Hz)。MNP 簇通过表面行走沿着定制丙烯酸托盘的仿生通道移动。使用摄像分析了不同距离和细胞涂层对 MNP 速度的影响。染料(作为药物替代品)和药物依托泊苷通过沿通道旋转 10 厘米距离的 MNP 进行运输。
结果:可以从磁分离时间预测 MNP 平移速度。与磁铁的距离或方向的变化会导致 MNP 速度的变化。HeLa、U251、U87 和 E297 细胞上最快 MNP 的平均速度分别为 0.24 ± 0.02、0.26 ± 0.02、0.28 ± 0.01 和 0.18 ± 0.03 cm/sec。U138 细胞显示出显着的 MNP 粘附性,沿通道 5.5 cm 处的速度降低了 87.1%。染料递送有助于将 MNP 作为药物递送的微型装置的效果可视化。MNP 簇的染料输送比扩散快 21.7 倍。MNPs 成功地加速了依托泊苷的递送,同时保留了化疗效果。
结论:此处描述的体外系统有助于通过旋转 MNP 簇在人体范围内对​​药物输送进行并排比较。如所提议的,这种微型装置具有在各种临床环境中增强药物输送的潜力。

更新日期:2020-06-11
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