The antibacterial effectiveness of fourth-generation poly-amidoamine dendrimers-loaded with amoxicillin in combating methicillin-resistant Staphylococcus aureus

In the community and in healthcare, methicillin-resistant Staphylococcus aureus (MRSA) is a major concern. Numerous infections with significant rates of morbidity and mortality are caused by MRSA strains worldwide. The widespread synthesis of virulence components is what makes MRSA so successful. The increasing resistance of MRSA to conventional antibiotics necessitates urgent exploration of alternative treatment strategies. One promising approach involves the use of fourth-generation poly-amidoamine dendrimers (PAMAM) loaded with amoxicillin, a critical β-lactam antibiotic for treating Gram-positive infections, although its efficacy is hindered by MRSA resistance. This study investigates the application of PAMAM G4 with amoxicillin to address this resistance, thereby optimizing the use of amoxicillin and potentially reducing the time and costs associated with developing new therapeutic agents. The physicochemical characteristics of the formulation were assessed through various in vitro analyses, including zetasizer and transmission electron microscopy, revealing a particle size of 219 nm, a zeta potential of -19 mV, and drug enacpsulation efficiency of 90.31%. The G4-amoxicillin dendrimer exhibited significant antibacterial activity, with a minimum inhibitory concentration of 0.25 mg/ml, as evidenced by growth assays in comparison to blank G4 and amoxicillin alone. Furthermore, the formulated nanoparticles demonstrated a substantial inhibition zone in the Kirby-Bauer Disk Diffusion method and exhibited strong anti-virulence properties, inhibiting 70% of biofilm formation and completely preventing hemolytic activity in MRSA, as shown in hemolysis assays. The formulated nanoparticles showed an effective antibacterial and anti-virulence activity against MRSA. Overall, the study added an evidence for a potential strategy to treat S. aureus and MRSA infection using nanoparticles and a potential reuse of amoxicillin.