双频超声遥控的中药配伍共晶-微霰弹枪递送系统克服耳生理屏障抗中耳感染的研究

鼓膜是耳部重要的生理屏障，如何克服鼓膜将中药有效组分最大程度地输送至中耳病灶部位，而又尽量减少对鼓膜的损伤，已成为抗中耳感染一个亟待解决的关键问题。本项目在前期研究基础上，把传统配伍应用中药的抗菌抗炎有效组分姜黄素和丹参酮IIA制成配伍共晶，作为“子弹”装载于自主设计的“微霰弹枪”给药装置，磁场控制方向，超声为“扳机”，发射中药共晶穿透鼓膜进入中耳，同时利用姜黄素自身的声敏特性，将声动力疗法与化学疗法有机结合，实现多功能协同抗菌，用于中耳炎的治疗。该系统将共晶作为中药组分配伍应用的有效形式，充分发挥其协同增效作用，而且通过双频超声远程控制，在尽量不破坏鼓膜的前提下实现中药复方组分的高效跨膜递送，并增强其抗菌能力，进一步提高抗中耳感染效果。本项目不仅为中药在中耳疾病治疗中的广泛应用提供新的输送平台，具有较高的临床应用价值，也为设计可克服体内生理屏障、安全有效的中药新型递药系统提供新的思路。

The tympanic membrane is an important physiological barrier of the ear, which is the first line of defense against pathogen invasions, but presents as a critical obstacle to drug delivery. In the treatment of middle ear infections, how to overcome the tympanic membrane and to improve the distribution at the lesion site of traditional Chinese medicine (TCM) with minimally invasive approaches, has become an urgent problem to be solved. On the basis of our previous findings, we will construct a “microshotgun” delivery system loaded with cocrystal complex of TCM compound components, which is able to cross the tympanic membrane. The efficient penetration can be powered by the gas generating reactions of perfluorocarbon emulsion under ultrasonic triggering. The cocrystal loaded in the microshotgun can actively penetrate the tympanic membrane using external magnetic field as directional control to align the microshotgun. Acting as antibacterial and anti-inflammatory agents, curcumin and tanshinone IIA are going to be employed as model drugs. The cocrystal composed of curcumin and tanshinone IIA will be designed and fabricated, which can significantly improve the solubility and play a good synergistic antibacterial effect. Furthermore, the cocrystal can be applied to the treatment of otitis media using the sonodynamic antibacterial chemical therapy mediated by the ultrasound-sensitive curcumin, which will further exert the synergistic antibacterial effect and build a better antibacterial performance. The microshotgun delivery system loaded with the TCM cocrystal which is remotely controlled by dual-frequency ultrasound, may be promising for future clinical applications. Precisely controlled administration with minimized trauma to the tympanic membrane represents the future perspective in middle ear drug research and development. This efficient and safe micro device will not only provide a new delivery platform for the treatment of diseases in the middle ear, but also hold potential to overcome the physiologic barriers in the body of TCM compound prescription.