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Magnetically responsive layer-by-layer microcapsules can be retained in cells and under flow conditions to promote local drug release without triggering ROS production
Nanoscale ( IF 5.8 ) Pub Date : 2020/03/25 , DOI: 10.1039/c9nr10329e
Jordan E. Read 1, 2, 3, 4, 5 , Dong Luo 6, 7, 8, 9 , Tina T. Chowdhury 3, 4, 5, 10, 11 , Rod J. Flower 1, 2, 3, 4, 5 , Robin N. Poston 2, 3, 4, 5, 12 , Gleb B. Sukhorukov 3, 4, 5, 10, 11 , David J. Gould 1, 2, 3, 4, 5
Affiliation  

Nanoengineered vehicles have the potential to deliver cargo drugs directly to disease sites, but can potentially be cleared by immune system cells or lymphatic drainage. In this study we explore the use of magnetism to hold responsive particles at a delivery site, by incorporation of superparamagnetic iron oxide nanoparticles (SPIONs) into layer-by-layer (LbL) microcapsules. Microcapsules with SPIONs were rapidly phagocytosed by cells but did not trigger cellular ROS synthesis within 24 hours of delivery nor affect cell viability. In a non-directional cell migration assay, SPION containing microcapsules significantly inhibited movement of phagocytosing cells when placed in a magnetic field. Similarly, under flow conditions, a magnetic field retained SPION containing microcapsules at a physiologic wall shear stress of 0.751 dyne cm−2. Even when the SPION content was reduced to 20%, the majority of microcapsules were still retained. Dexamethasone microcrystals were synthesised by solvent evaporation and underwent LbL encapsulation with inclusion of a SPION layer. Despite a lower iron to volume content of these structures compared to microcapsules, they were also retained under shear stress conditions and displayed prolonged release of active drug, beyond 30 hours, measured using a glucocorticoid sensitive reporter cell line generated in this study. Our observations suggest use of SPIONs for magnetic retention of LbL structures is both feasible and biocompatible and has potential application for improved local drug delivery.

中文翻译:

磁响应的逐层微胶囊可以保留在细胞中并在流动条件下促进局部药物释放而不会触发ROS的产生

纳米工程车辆具有将载药直接运送到疾病部位的潜力,但可以通过免疫系统细胞或淋巴引流清除。在这项研究中,我们通过将超顺磁性氧化铁纳米颗粒(SPIONs)掺入逐层(LbL)微胶囊中,探索了利用磁性将反应性颗粒保持在递送位点的方法。具有SPIONs的微胶囊可被细胞快速吞噬,但在递送后24小时内不会触发细胞ROS的合成,也不会影响细胞活力。在无方向性细胞迁移测定中,含有SPION的微胶囊在置于磁场中时会显着抑制吞噬细胞的运动。类似地,在流动条件下,磁场保留的SPION含有微囊,其生理壁切应力为0.751达因厘米−2。即使当SPION含量降低到20%时,大多数微囊仍然保留着。地塞米松微晶是通过溶剂蒸发合成的,并经过包含SPION层的LbL封装。尽管与微胶囊相比,这些结构的铁含量较低,但它们仍保留在剪切应力条件下,并在本研究中产生的对糖皮质激素敏感的报告细胞系中测定,超过30小时显示出活性药物的长时间释放。我们的观察结果表明,将SPIONs用于LbL结构的磁性保留既可行又具有生物相容性,并且在改善局部药物输送方面具有潜在的应用前景。
更新日期:2020-04-09
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