清除铜绿假单胞菌生物被膜及分散细菌且防治并发症的自驱动微纳米马达递药系统的功能研究

铜绿假单胞菌（P. aeruginosa, PA）所致顽固性肺部感染严重危害人类健康。生物被膜（Biofilm, BF）的形成是造成感染持续和细菌耐药的关键，降解BF虽然有助于提高PA清除率，但降解BF引起的大量细菌突然扩散可能诱发致命性全身感染。如何安全有效地治疗PA所致顽固性肺部感染并防治分散细菌引起的并发症是目前亟须解决的科学问题。前期发现，基于脂质体递药系统的肺部吸入环丙沙星可有效提高肺局部药物浓度及杀菌效果，一氧化氮可有效分散BF。项目拟构建肺部吸入自驱动微纳米马达载脂质体递药系统，系统不断释放的一氧化氮为穿透黏液层提供动力并分散BF，脂质体包载的环丙沙星清除分散细菌，羟基喹啉抑制细菌扩散传播。项目拟系统研究分散BF抗菌疗法的安全性和有效性并研发治疗PA感染的新型递药系统，为临床治疗PA所致顽固性肺部感染提供新策略。

Refractory pulmonary infections caused by P. aeruginosa seriously endanger human health. The formation of biofilm is the key to the persistent infection and bacterial resistance. Although degrading biofilm helps to improve the clearance rate of P. aeruginosa, the sudden spread of many bacteria caused by degrading biofilm may induce fatal systemic infections. How to safely and effectively treat intractable lung infections caused by P. aeruginosa and prevent the complications caused by dispersed bacteria is a scientific problem that needs to be solved urgently. In the previous studies, it was discovered that the inhalable ciprofloxacin loaded liposomal delivery system can effectively increase the local drug concentration and bactericidal effect in the lung. Meanwhile, nitric oxide can effectively disperse biofilm. The project plans to develop an inhaled self-propelled micro/nanomotors drug delivery system loading ciprofloxacin and hydroxyquinoline. Constant release of nitric oxide by the system provides power for penetrating the mucus layer and disperses biofilm. The ciprofloxacin can remove dispersed bacteria and hydroxyquinoline can inhibit the spread of dispersed bacteria. The project intends to systematically study the safety and effectiveness of degrading biofilm antibacterial therapy and develop a new drug delivery system for the treatment of P. aeruginosa infections. Finally, this project could provide a new strategy for the clinical treatment of P. aeruginosa-associated refractory pulmonary infections.