Neuraminidase and pH responsive nano-drug against resistant Glaesserella parasuis

Glaesserella parasuis (GPS) infection leads to significant economic losses in livestock, with antibiotic resistance exacerbating the issue. The lengthy development cycle of new drugs further complicates timely intervention. Neuraminidase, a virulence factor of GPS, plays a critical role in infection progression. This study presents PSA-Gly-TD, a dual-responsive nanomicelle drug delivery system designed to target neuraminidase and pH variations, offering a solution to the problem of drug-resistant GPS infections. By covalently linking polysialic acid with Tildipirosin, nanoparticles with excellent dispersibility, stability, and a drug encapsulation efficiency of 99.27 % were synthesized. The system demonstrated a particle size of 64.75 nm, accelerated drug release in pathological conditions, and significantly enhanced cellular uptake-nearly three times higher than Tildipirosin alone while maintaining cell viability above 90 %. PSA-Gly-TD preserved the antibacterial efficacy of Tildipirosin and exhibited superior bactericidal activity against drug-resistant GPS strains. In animal models, PSA-Gly-TD showed a stable metabolic profile, reduced tissue damage, and avoided hemolysis, making it a safe and effective option for treating drug-resistant bacterial infections. These results underscore PSA-Gly-TD as a promising therapeutic agent, offering an innovative approach to combating antimicrobial resistance in veterinary medicine and addressing critical challenges in livestock health.