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 necessitating new antibacterial strategies. In this study, a pH-responsive carrier-free nanoparticles (BF-TEI NPs) are fabricated based on the Schiff-based 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 the 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 both in vitro and in vivo good biocompatibility and safety evaluation of BF-TEI NPs. The carrier-free self-assembly strategy of clinical antibiotics offers an innovative approach to overcome drug resistance and improve infectious wound healing.