Polymyxin B-Modified Fosfomycin Liposomes Target Gram-Negative Bacteria and Exert Synergistic Antibacterial Effect

Area of Science:

• Microbiology
• Nanotechnology
• Pharmacology

Background:

• Bacterial infections pose a significant global health threat, necessitating improved therapeutic strategies.
• Traditional antibiotic delivery faces challenges in efficacy and drug resistance, with poor targeting efficiency.
• Achieving simultaneous therapeutic drug concentrations in target tissues is difficult due to differing drug metabolism.

Purpose of the Study:

• To construct bacteria-targeted liposomes for enhanced antibiotic delivery and treatment efficacy.
• To develop polymyxin B (PMB)-adsorbed liposomes carrying fosfomycin (FOS) for targeted delivery to Acinetobacter baumannii.
• To evaluate the therapeutic efficacy, antibacterial activity, and safety profile of the novel drug delivery system.

Main Methods:

• Anionic liposomes were prepared using the thin-film dispersion method.
• Cationic polymyxin B (PMB) was adsorbed onto liposome surfaces via electrostatic interactions, encapsulating fosfomycin (FOS).
• In vitro and in vivo studies assessed PMB-liposome targeting, PMB-FOS-liposome efficacy, and PMB nephrotoxicity.

Main Results:

• PMB-liposomes demonstrated effective in vitro and in vivo targeting of Acinetobacter baumannii.
• PMB-FOS-liposomes exhibited superior therapeutic efficacy compared to a mixture of free PMB and FOS.
• Adsorption of PMB onto liposomes significantly reduced its associated nephrotoxicity in mice.

Conclusions:

• PMB-liposomes provide effective targeting of Acinetobacter baumannii.
• Encapsulated fosfomycin within PMB-liposomes demonstrates synergistic antibacterial activity and enhanced efficacy.
• This liposomal drug delivery approach reduces adverse drug reactions, offering a promising strategy for bacterial infections.