pH-Responsive carrier-free nanoparticles based on teicoplanin and borneol for enhanced MRSA infectious wound healing

Abstract

Bacterial infections severely threaten human health, and the drug resistance induced by long-term high-dose antibiotic use is a critical issue, which necessitates new antibacterial strategies. In this study, pH-responsive carrier-free nanoparticles (BF–TEI NPs) are fabricated based on the Schiff-base bonding between the hydrophilic antibiotic teicoplanin (TEI) and the hydrophobic antibacterial borneol 4-formylbenzoate (BF). Self-assembled BF–TEI NPs enable synchronous release of BF and TEI in infected sites for synergistic antibacterial effects via acidic microenvironment-triggered Schiff-base bond cleavage. Compared with the physical mixture of BF and TEI, BF–TEI NPs show lower in vitro minimum inhibitory and bactericidal concentrations against Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA), indicating enhanced antibacterial activity. Moreover, BF–TEI NPs effectively eliminate MRSA at the in vivo infected sites and accelerate wound healing. Considering the good in vitro and in vivo biocompatibility and safety of BF–TEI NPs, the carrier-free self-assembly strategy of clinical antibiotics offers an innovative approach for overcoming drug resistance and improving infectious wound healing.