Armored polymyxin B: a nanosystem for combating multidrug-resistant Gram-negative bacilli

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Infectious Diseases

Background:

• Bacterial infections, particularly those caused by multidrug-resistant (MDR) strains, pose a significant global health threat.
• Polymyxin B (PMB) is a crucial antibiotic for treating Gram-negative bacterial infections but faces limitations due to poor lung penetration and dose-dependent toxicity.

Purpose of the Study:

• To develop a targeted nanodrug delivery system to improve the efficacy and safety of Polymyxin B for treating MDR bacterial pneumonia.
• To evaluate the therapeutic potential of a novel biomimetic nanocarrier for combating lung infections.

Main Methods:

• A targeted nanodrug delivery system, PMB@HMnO2@NM, was engineered using hollow mesoporous manganese dioxide nanoparticles coated with neutrophil membranes.
• The system's efficacy was assessed in a mouse model of acute pneumonia induced by multidrug-resistant *Pseudomonas aeruginosa*.

Main Results:

• PMB@HMnO2@NM demonstrated targeted delivery to bacterial aggregates and infected lung tissues.
• The nanodrug formulation significantly improved survival rates and reduced lung inflammation compared to free PMB.
• No significant nephrotoxicity or neurotoxicity was observed with the nanodrug treatment.

Conclusions:

• The PMB@HMnO2@NM nanodrug delivery system offers a promising strategy for enhancing the treatment of MDR bacterial infections, particularly pneumonia.
• Biomimetic nanocarriers can overcome the limitations of conventional antibiotics, providing a foundation for developing next-generation antibacterial therapies.