An easy-to-prepare microshotgun for efficient transmembrane delivery by powering nanoparticles
An easy-to-prepare microshotgun for efficient transmembrane delivery by powering nanoparticles
复制标题
一种易于制备的微霰弹枪，通过为纳米颗粒提供动力实现高效跨膜输送
DOI：
10.1016/j.jconrel.2020.02.016
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发表时间：
2020-05-10
影响因子：
10.8
通讯作者：
Chen, Gang
中科院分区：
文献类型：
--
作者：
Liang, Zhongping;Yu, Hang;Chen, Gang
生物屏障是抵御病原体入侵的第一道防线，但它们也可能成为药物递送的关键障碍。尽管最近已经制定了各种策略来克服它们，但仍然需要做出重大努力来实现更安全和更有效的药物递送。在此，我们构建了一种不含金属的“细腰”形微型鸟枪递送装置，其能够穿过鼓膜和圆窗膜。有效的渗透是由自含化学品的气体生成反应提供动力的。该装置在几个方面是有利的。首先，该装置可以使用简单的程序、普通的设备和负担得起的材料来制备。其次，该器械被认为具有生物相容性，单次/重复给药后细胞毒性低，血细胞参数和组织学形态正常。第三，装载在微型鸟枪中的纳米颗粒在第一次加速后能够主动穿透膜的上皮层，并且可以利用外部磁场作为次级动力来对准和加速纳米颗粒而穿透鼓膜的内皮层。此外，高分辨扫描电镜观察到，微鸟枪所引起的膜微穿透可以在短时间内恢复。这种易于获得、有效且安全的微型装置为治疗中耳和内耳疾病提供了新的输送平台，并具有克服体内生理障碍的潜力。
Biological barriers are the first line of defense against pathogen invasions, but they can also present as critical obstacles to drug delivery. Despite a variety of strategies have been developed recently to overcome them, significant efforts are still needed to achieve safer and more effective drug delivery. Herein, we constructed a metal-free, "slim waist" shaped microshotgun delivery device, which was able to cross the tympanic membrane and round window membrane. The efficient penetration was powered by the gas generating reactions of self-contained chemicals. This device is advantageous in several aspects. First, the device could be prepared using simple procedures, common equipment and affordable materials. Second, the device is deemed biocompatible, revealed by low cytotoxicity, normal blood cell parameters and histological morphology after single/repeated administration. Third, the nanoparticles loaded in the microshotgun were able to actively penetrate the epithelial layer of the membrane after the first acceleration, and can penetrate the endothelial layer of tympanic membrane using external magnetic field as the secondary power to align and accelerate the nanoparticles. In addition, the micro-penetration of membrane induced by microshotgun could recover in a short time as observed in high-resolution scanning electron microscopy. This easy-to-get, efficient and safe micro device provides a new delivery platform for the treatment of diseases in the middle ear and inner ear, and holds potential to overcome the physiologic barrier in the body.