School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, China.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
J Control Release. 2020 May 10;321:119-131. doi: 10.1016/j.jconrel.2020.02.016. Epub 2020 Feb 6.
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.
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输送的关键障碍。尽管最近已经开发出多种克服这些障碍的策略，但仍需要做出重大努力以实现更安全、更有效的药物输送。在这里，我们构建了一种无金属的“细腰”形状的微枪输送装置，该装置能够穿透鼓膜和圆窗膜。高效穿透的动力来自于自包含化学物质的产气反应。该装置具有几个方面的优势。首先，该装置可以使用简单的程序、常见的设备和负担得起的材料来制备。其次，该装置被认为是生物相容的，通过单次/重复给药后的低细胞毒性、正常血细胞参数和组织形态学来证明。第三，负载在微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，并且可以在外磁场作为二次动力来对齐和加速纳米颗粒时穿透鼓膜的内皮层。此外，如高分辨率扫描电子显微镜观察到的，微枪引起的膜微渗透可以在短时间内恢复。这种易于获得、高效和安全的微装置为中耳和内耳疾病的治疗提供了一个新的输送平台，并有可能克服体内的生理屏障。
