An easy-to-prepare microshotgun for efficient transmembrane delivery by powering nanoparticles.

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.