Antioxidant-antiinflammatory dual-pathway synergistic therapy: An intelligent polysialic acid nano-delivery platform against Glaesserella parasuis.

Glaesserella parasuis infection often triggers an out-of-control inflammatory cascade. This can lead to severe tissue damage and ultimately result in higher mortality. Tildipirosin (TD) has both bactericidal and anti-inflammatory effects. But TD still has some issues in clinical practice. It is challenging to deliver the drug precisely to the site of infection, which can result in insufficient local drug concentration at the lesion. At the same time, its ability to regulate abnormal inflammatory responses is relatively limited. To address the above issues, we developed a drug nanodelivery system (PSA@PBE). This system can respond simultaneously to neuraminidase (NA) secreted by Glaesserella parasuis infection and the excessive reactive oxygen species (ROS) generated by oxidative stress. This system is capable of programmable drug release. Subsequently, we systematically studied the physicochemical properties of the nanoparticles, their in vitro drug release behavior, and the cellular uptake efficiency. Experimental results showed that the drug loading of the nanoparticles was 20.75% ± 0.46%. The drug encapsulation efficiency was 88.16% ± 0.96%. The drug could be released in vitro for about 30 h. The cellular uptake rate could reach about 85%. Both in vitro and in vivo experimental results show that PSA@PBE-TD nanoparticles have significant antibacterial effects. They can also reduce the release of inflammatory cytokines. The improvement in these therapeutic effects is attributed to their synergistic mechanisms. On one hand, the nanomaterials themselves can scavenge reactive free radicals, reducing damage caused by oxidative stress. On the other hand, TD exerts its effect after being released at the site of infection. The two components work together synergistically to enhance the overall therapeutic effect. In summary, the drug delivery nanoplatform we designed is capable of effectively carrying drugs and releasing them into cells. It can slowly release drugs and effectively combat Glaesserella parasuis infections. It can efficiently kill bacteria, clear harmful molecules, and reduce inflammation. This approach represents a novel and effective way to treat this type of infection.