Sonication-Assisted Self-Assembled Resveratrol Nanoparticles\nwith Enhanced Antiviral and Anti-inflammatory Activity against Respiratory\nSyncytial Virus-Induced Pneumonia

Respiratory syncytial virus (RSV)-induced\nviral pneumonia in children\nis common worldwide. Its high occurrence and lack of an effective\nvaccine make it a leading cause of death in children. Severe RSV infection\ncan trigger uncontrolled inflammatory responses in patients, so the\ndevelopment of small molecule drugs with the dual function of “direct\nantivirus” and “inflammatory response regulation”\nis welcome. Resveratrol (Res) has been reported to have antiviral\nand anti-inflammatory pharmacological effects, but its application\nis limited because of its poor water solubility and oral bioavailability.\nBased on small-molecule nanotechnology, we developed a sonication-assisted\nself-assembly method for preparing insoluble Res into highly soluble\nresveratrol nanoparticles (Res NPs). The obtained Res NPs exhibited\na higher water solubility and a faster dissolution rate, which was\nmore conducive to the effectiveness of Res in addressing RSV-induced\nviral pneumonia. In vitro studies had shown that Res NPs played an\nantiviral role by inhibiting RSV replication and reducing the production\nof pro-inflammatory cytokines. Nebulized inhalation administration\nof Res NPs prolonged the drug’s residence time in the lungs,\nwhich appears to increase the accumulation and effectiveness of Res\nNPs. Additionally, in vivo studies had demonstrated significant benefits\nof Res NPs in inhibiting RSV viral load and improving the pulmonary\nmicroenvironment in RSV-infected mice. Both antiviral and anti-inflammatory\nexperiments had confirmed that the pharmacological activity of Res\nNPs is superior to that of Res. This suggested that nanosizing Res\nwas an effective way to enhance the original pharmacological activity\nof Res and also offered a new formulation strategy for treating viral\npneumonia.