Hydrogen Peroxide-Activated Nitric Oxide-Releasing Vancomycin-Loaded Electrostatic Complexation for Efficient...

Area of Science:

• Biomedical Engineering
• Drug Delivery Systems
• Antimicrobial Research

Background:

• Subcutaneous abscess treatment is challenged by drug-resistant bacteria, notably methicillin-resistant Staphylococcus aureus (MRSA).
• Nitric oxide (NO) shows promise for enhancing antimicrobial therapies, but its gaseous nature complicates precise delivery and controlled release.
• Existing treatments often require complementary strategies to overcome antibiotic resistance and improve efficacy.

Purpose of the Study:

• To develop an on-demand, hydrogen peroxide (H2O2)-activated nitric oxide (NO)-releasing system for treating subcutaneous abscesses.
• To fabricate and characterize a vancomycin (Van)-loaded electrostatic complexation system (Lipo/Van@Arg) for enhanced drug delivery.
• To evaluate the in vitro and in vivo efficacy of the developed system against MRSA-induced subcutaneous abscesses.

Main Methods:

• Fabrication of vancomycin-loaded liposomes (Lipo/Van) and their electrostatic complexation with l-arginine (Lipo/Van@Arg).
• In vitro assessment of bacterial binding, biofilm penetration, and NO release triggered by H2O2.
• In vivo evaluation of Lipo/Van@Arg efficacy in a BALB/c mouse model of MRSA-induced subcutaneous abscesses.

Main Results:

• Lipo/Van@Arg demonstrated enhanced bacterial binding and biofilm penetration capabilities.
• The system effectively released NO upon encountering endogenous H2O2 within biofilms.
• Combined NO and Van treatment via Lipo/Van@Arg successfully eliminated MRSA and prevented abscess recurrence in vivo.

Conclusions:

• The developed Lipo/Van@Arg system enables controlled NO delivery and precise release, offering a promising strategy for abscess treatment.
• This approach synergistically combines the effects of NO and Vancomycin for potent antibacterial and biofilm eradication.
• The study highlights significant clinical implications for improving the efficiency of subcutaneous abscess treatment, particularly against resistant strains.