Nebulized pH-Responsive Nanospray Combined with Pentoxifylline and Edaravone to Lungs for Efficient Treatments of Acute Respiratory Distress Syndrome

Abstract

Abstract Background The COVID-19 pandemic has become an unprecedented global medical emergency, resulting in millions of people being infected with the COVID-19 virus and more than 5 million deaths. Acute respiratory distress syndrome (ARDS) caused by COVID-19 is the most common serious complication leading to death. However, no treatment has been proved successful in treating ARDS apart from the low tidal volume mechanical ventilation. Herein, we have constructed a novel nanospray with anti-inflammatory and antioxidant capacity by loading Pentoxifylline (PTX) and Edaravone (Eda) on ZIF-8. This nanospray was endowed with synergetic therapy ability, which could kill two birds with one stone: the loaded PTX played a powerful anti-inflammatory role by inhibiting the activation of inflammatory cells and the synthesis of pro-inflammatory cytokines, meanwhile, Eda was responsible for free radical scavenger in ARDS. Results These data showed ZIF8-EP protected RAW264.7 cells from oxidative stress-induced apoptosis by removing excessive ROS in cells. In the mice model of LPS-induced ARDS, ZIF8-EP nanospray appreciably inhibited the inflammatory response and weakened the oxidative stress, and efficiently controlled the damage of ARDS to lung tissue. Subsequently, WB, IHC, RT-qPCR and Elisa experiments verified the main mechanism of ZIF8-EP nanospray inhibiting ARDS inflammation. Conclusion Taken together, compared with free PTX and Eda the nanospray was proved to have excellent therapeutic effect on ARDS in vitro and in vivo without hematotoxicity and systemic toxicity.