Nanotechnology Meets superbugs: biocompatible polymeric nanoparticles combat MDR Klebsiella pneumoniae via gene suppression and biofilm Inhibition.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a critical threat in healthcare settings due to its limited treatment options and high resistance to conventional antibiotics. This study explores the potential of polycaprolactone (PCL) nanospheres as a delivery vehicle for imipenem to combat multidrug-resistant CRKP. Imipenem-loaded nanospheres, with an average size of 610 ± 125 nm and an encapsulation efficiency of 84.5%, were synthesized using a double-emulsion method and characterized for morphology, size, drug loading, and release profile. The formulation demonstrated a substantial improvement in antibacterial activity, with an eightfold reduction in minimum inhibitory concentration compared to free imipenem. The nanoparticles also significantly inhibited biofilm formation and accelerated bacterial killing. Molecular analysis showed marked suppression of key resistance genes. Additionally, cytotoxicity assays confirmed high biocompatibility, with over 80% viability in fibroblast cells. These findings indicate that PCL-based nanocarriers enhance the efficacy and safety profile of imipenem, offering a promising strategy for addressing antibiotic resistance in CRKP.