Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates.

Abstract

Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineering neutrophil nanovesicles with cholesterols to deliver DEX for enhanced treatment of COVID-19. Relying on surface chemokine and cytokine receptors, the iSEND showed improved targeting to macrophages and neutralized broad-spectrum cytokines. The nanoDEX, made by encapsulating DEX with the iSEND, efficiently promoted the anti-inflammation effect of DEX in an acute pneumonia mouse model and suppressed DEX-induced bone density reduction in an osteoporosis rat model. Relative to an intravenous administration of DEX at 0.1 milligram per kilogram, a 10-fold lower dose of nanoDEX administered by inhalation produced even better effects against lung inflammation and injury in severe acute respiratory syndrome coronavirus 2-challenged nonhuman primates. Our work presents a safe and robust inhalation delivery platform for COVID-19 and other respiratory diseases.

• Authors: Qian-Fang Meng, Wanbo Tai, Mingyao Tian, Xinyu Zhuang, Yuanwei Pan, Jialin Lai, Yangtao Xu, Zhiqiang Xu, Min Li, Guangyu Zhao, Guang-Tao Yu, Guocan Yu, Rongchang Chen, Ningyi Jin, Xiao Li, Gong Cheng, Xiaoyuan Chen, Lang Rao
• Journal: Science advances (Sci Adv) Vol. 9 Issue 24 Pg. eadg3277 (06 16 2023) ISSN: 2375-2548 [Electronic] United States
• PMID: 37315135 (Publication Type: Journal Article)

Chemical References

• Dexamethasone

Topics

• Mice
• Rats
• Animals
• COVID-19
• Cytokine Release Syndrome (drug therapy, etiology)
• COVID-19 Drug Treatment
• Nanoparticles
• Dexamethasone (pharmacology, therapeutic use)
• Primates