Polydopamine-coated mesoporous silica nanoparticles co-loaded with Ziyuglycoside I and Oseltamivir for synergistic treatment of viral pneumonia

Viral pneumonia (VP) is a serious health risk to humans, however, there is still a lack of specific treatments for VP. The spread of the virus in the body induces an excessive inflammatory response that can cause chronic or irreversible damage to lungs. Hence, VP treatment requires rapid clearance of the virus and sustained inflammation control. In this study, an innovative mesoporous silica medication delivery system co-loaded with Ziyuglycoside I(ZgI) and Oseltamivirv(OST) in fast and slow monomeric forms ZgI@MSNs-OST@ Polydopamine (PDA) was prepared for targeted treatment of VP. The prepared ZgI@MSNs-OST@PDA nanoparticles had a homogeneous and membrane-encapsulated spherical structure, with an average particle size of approximately 760 nm. in vitro release and in vivo pharmacokinetic studies demonstrated that ZgI@MSNs-OST@PDA achieved immediate release of OST and sustained release of ZgI, which was readily taken up by the cells. In vitro anti-H1N1 virus experiments showed that nanoparticles rapidly killed the virus in host cells, and the anti-inflammatory effect was sustained and long-lasting, providing excellent protection to host cells. In vivo antiviral pneumonia experiments confirmed the rapid clearance of influenza viruses from mouse lungs and the effective control of overactivated immune responses by ZgI@MSNs-OST@PDA nanoparticles. Through a mechanistic study, we found that the treatment of viral pneumonia with nanoparticles was associated with inhibition of the NLRP3 inflammasome pathway. In conclusion, the constructed nanoparticles achieved synergistic therapeutic effects of ZgI and OST on VP, that is, rapid killing of influenza viruses by OST and effective control of the virus-induced hyperinflammatory response by ZgI.