Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates.
Sci Adv
; 9(24): eadg3277, 2023 06 16.
Article
in En
| MEDLINE
| ID: mdl-37315135
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nanoparticles
/
COVID-19
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Sci Adv
Year:
2023
Document type:
Article
Affiliation country:
China