Boost antibacterial and promote wound healing effects of topical dermal nanosystem against MRSA infection

• A novel topical dermal nanosystem of benzalkonium bromide was developed, exhibiting favorable physicochemical properties. • It demonstrated enhanced anti-biofilm efficacy, inhibiting biofilm formation and eradicating mature biofilms in vitro. • Furthermore, it significantly promoted wound healing in skin infections caused by multidrug-resistant Staphylococcus aureus. • TMT proteomics reveals it could increase activity of membrane transporters and decrease metabolism of amino acid and proteins. Wound infections caused by MRSA continue to threaten human health and pose large economic burdens on global healthcare. The use of nanosystem technology is important for controlling bacterial resistance, offering multiple benefits such as thermodynamic stability and good biocompatibility. Herein, we report a novel dermal nanosystem, ZSE, loaded with benzalkonium bromide, with desirable characteristics such as an average size of 23.47 ± 10.1 nm, a zeta potential (ζ) of 39.3 ± 5.53 mV, and a PDI of 0.153, that was generated via the low-energy emulsification technique. ZSE exhibited excellent stability in the TEM, AFM, FTIR, DSC, and TG analyses. Furthermore, compared to benzalkonium bromide alone, it demonstrated greater and faster antibacterial activity against MRSA in vitro , promoting wound healing by reducing bacterial colonization and regulating the levels of inflammatory cytokines. Moreover, this system inhibited biofilm formation and eradicated mature biofilms while accelerating the degradation and damage of cell membranes. Notably, the dual effects of ZSE, characterized by increased activity of membrane transporters and decreased metabolism of amino acid and proteins, were discovered using quantitative TMT proteomics. This work suggested that a topical dermal self-nanoemulsion system loaded with benzalkonium bromide could become a promising formulation for wound healing caused by MRSA infection.