PEGylated ofloxacin nanoparticles render strong antibacterial activity against many clinically important human...

Area of Science:

• Pharmacology
• Nanotechnology
• Microbiology

Background:

• Bacterial resistance to antibiotics like ofloxacin is a growing clinical concern.
• Mechanisms of resistance include target mutations, reduced permeability, and increased drug efflux.
• Strategies to enhance drug uptake and reduce efflux are crucial for effective treatment.

Purpose of the Study:

• To compare the efficacy of free ofloxacin (OFX) with nanoformulated OFX (OFX-PLGA and OFX-mPEG-PLGA) in terms of bacterial uptake and antibacterial activity.
• To evaluate the potential of mPEG-PLGA nanoencapsulation in preventing antibiotic resistance development.

Main Methods:

• Synthesis and characterization of poly(lactic-co-glycolic acid) (PLGA) and methoxy poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles encapsulating ofloxacin (OFX).
• Assessment of bacterial uptake and in vitro antibacterial activity against key human pathogens (E. coli, P. vulgaris, S. typhimurium, P. aeruginosa, K. pneumoniae, S. aureus).
• Evaluation of Bacillus subtilis resistance development against OFX in the presence of mPEG-PLGA nanoencapsulation.

Main Results:

• Both OFX-PLGA and OFX-mPEG-PLGA nanoformulations demonstrated improved bacterial uptake and antibacterial activity compared to free OFX.
• OFX-mPEG-PLGA exhibited significantly higher bacterial uptake and antibacterial efficacy than OFX-PLGA against all tested pathogens.
• mPEG-PLGA nanoencapsulation effectively inhibited the development of ofloxacin resistance in Bacillus subtilis.

Conclusions:

• mPEG-PLGA nanoformulations represent a promising strategy to overcome bacterial resistance to fluoroquinolones like ofloxacin.
• Enhanced drug delivery via mPEG-PLGA nanoparticles improves antibacterial efficacy and prevents resistance emergence.
• This nanotechnology-based approach holds potential for developing more effective antibiotic therapies.