Meropenem incorporated nanoflowers as nano antibiotics: A promising strategy for combating antimicrobial resistance and biofilm-associated infections

Antimicrobial resistance (AMR) poses a significant global health threat, with biofilm formation playing a critical role in reducing antibiotic efficacy. This study aims to develop an innovative nanomaterial-based approach to combat AMR by synthesizing meropenem-based nanoflowers (mNFs) and evaluating their antibacterial and antibiofilm activities. The mNFs were synthesized via a simple self-assembly method and extensively characterized. Field Emission Scanning Electron Microscopy (FESEM) and Transmission Electron Microscopy (TEM) confirmed their distinct flower-like morphology with sizes ranging from 200-450 nm. Energy-Dispersive X-ray Spectroscopy (EDX) verified elemental composition, while X-Ray Diffraction (XRD) analysis revealed their crystalline structure. Dynamic Light Scattering (DLS) showed a hydrodynamic size of similar to 300 nm, and UV-Vis spectroscopy confirmed characteristic meropenem peaks, indicating successful nanoflower formation. The mNFs exhibited potent antibacterial activity against Pseudomonas aeruginosa PAO1, Staphylococcus aureus, and Klebsiella pneumoniae, with MIC50 values of 0.4 mg/mL for P. aeruginosa and K. pneumoniae, and 0.6 mg/mL for S. aureus. A significant reduction in colony-forming units (CFU/mL) was observed in P. aeruginosa cultures treated with mNFs compared to free meropenem. Confocal microscopy showed an increased ratio of dead cells post-treatment, while TEM images revealed substantial cell membrane disruption. Cell permeability assays further confirmed compromised bacterial membranes. Importantly, mNFs demonstrated robust anti-biofilm activity, achieving up to 84.54 % biofilm inhibition against P. aeruginosa PAO1 at 0.5 mg/mL. Additionally, the production of pyocyanin, a key virulence factor, was significantly reduced following treatment. In conclusion, this study introduces meropenem-based nanoflowers as a novel and effective strategy for tackling biofilm-associated infections and antimicrobial resistance. The combination of enhanced antibacterial efficacy, biofilm disruption, and virulence suppression positions mNFs as a promising therapeutic candidate for combating multidrug-resistant pathogens.