Infection-responsive polysaccharide-based drug-loaded nano-assembly for dual-modal treatment against drug-resistant bacterial lung infection

Abstract

The escalating issue of lung infections induced by multi-drug resistant (MDR) bacteria is threatening human health. Thus, the development of efficient drug delivery systems is essential to eliminate MDR bacterial lung infections effectively. Herein, we designed inhalable drug-loaded nano-assemblies by the electrostatic interaction between negatively charged sodium alginate and a positively charged antibacterial polymer, quaternized polyethyleneimine (QPEI-C₆), as well as a kind of typical antibiotic for therapy of lung infection, azithromycin (AZT). By adjusting the feed ratios, we optimized the size of the nano-assembly to approximately 200 nm (STQ₁₂), which was beneficial for penetration through the mucus layer and biofilm. In the slightly acidic environment of the infected site, the nano-assembly could dissemble responsively and release AZT and QPEI-C₆. Because of the combined bactericidal effect, STQ₁₂ exhibited high bactericidal efficiency against MDR bacteria. In animal experiments, STQ₁₂ showed notable efficacy against MDR bacterial lung infection. Gene transcriptomic results showed that the main effects of STQ₁₂ against bacteria were through influencing the bacterial cell components and metabolic processes, and affecting their growth and reproduction. This work provides a promising strategy to treat MDR bacterium-induced lower respiratory tract infections.