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

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 engineer...

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Published in:Science advances 2023-06, Vol.9 (24), p.eadg3277
Main Authors: Meng, Qian-Fang, Tai, Wanbo, Tian, Mingyao, Zhuang, Xinyu, Pan, Yuanwei, Lai, Jialin, Xu, Yangtao, Xu, Zhiqiang, Li, Min, Zhao, Guangyu, Yu, Guang-Tao, Yu, Guocan, Chen, Rongchang, Jin, Ningyi, Li, Xiao, Cheng, Gong, Chen, Xiaoyuan, Rao, Lang
Format: Article
Language:English
Subjects:
Animals
Biomedicine and Life Sciences
Coronavirus
COVID-19
COVID-19 Drug Treatment
Cytokine Release Syndrome - drug therapy
Cytokine Release Syndrome - etiology
Dexamethasone - pharmacology
Dexamethasone - therapeutic use
Mice
Nanoparticles
Primates
Rats
SciAdv r-articles
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Summary: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.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.adg3277