Cholesterol-Rich Antibiotic-Loaded Liposomes as Efficient Antimicrobial Therapeutics

Area of Science:

• Microbiology and Pharmaceutical Sciences
• Nanotechnology in Drug Delivery

Background:

• Liposomal antibiotics show improved efficacy over free drugs.
• Investigating liposome composition, concentration, and surface modification is crucial for optimizing antimicrobial activity.

Purpose of the Study:

• To evaluate the impact of cholesterol (Chol) content, liposome concentration, and polyethylene glycol (PEG) coating on moxifloxacin (MOX) liposome activity against Staphylococcus epidermidis (S.e).
• To assess MOX-liposomes against planktonic S.e and pre-formed biofilms.
• To characterize MOX-liposomes for loading, size, and zeta potential.

Main Methods:

• Liposomes with varying Chol content were prepared and characterized.
• Antimicrobial activity was assessed against planktonic bacteria and biofilms using growth inhibition, killing assays, live-dead staining, crystal violet, MTT assay, and confocal microscopy.
• In vivo efficacy was evaluated in a zebrafish bacteremia model.

Main Results:

• Liposomes exhibited nano-dimensions (92-114nm) with negative zeta potentials (-2.30mV to -4.50mV).
• Higher Chol content significantly enhanced MOX-liposome activity against planktonic S.e and biofilms.
• Increased liposome concentration boosted antimicrobial effects; PEGylation had no significant impact.
• Chol-rich liposomes demonstrated increased bacterial binding and reduced integrity in the presence of S. epidermidis.
• In vivo studies confirmed superior efficacy of Chol-rich MOX-liposomes over free moxifloxacin.

Conclusions:

• Cholesterol-rich liposomes significantly enhance the antimicrobial efficacy of moxifloxacin against S. epidermidis.
• Liposome concentration and cholesterol content are key factors in optimizing liposomal antibiotic performance.
• PEGylated and cholesterol-rich liposomal antibiotics show promise as advanced therapeutics for S. epidermidis infections.