Application of synergistic β-lactamase inhibitors and antibiotics in the treatment of wounds infected by superbugs

Abstract

• 4-Carboxyphenylboronic acid -modified Prussian blue nanoparticles (CPA NPs) were designed. • CPA NPs can restore the antibacterial activity of amoxicillin. • CPA NPs in vivo showed anti-infectious activity, and promoted wound healing of mice. Amoxicillin appears to be clinically drug-resistant due to the presence of β-lactamase in bacteria. Here, we designed and prepared a hollow Prussian Blue (HPB)-based therapeutic nanoplatform that was constructed by encapsulating amoxicillin into polyethyleneimine with β-lactamase inhibitor 4-carboxyphenylboronic acid (4-Cpba) decorated HPB nanoparticles (CPA NPs). The antibacterial effect of the CPA NPs on drug-resistant bacteria was observed by in vitro colony-forming unit, minimum inhibitory concentration, scanning electron microscopy, and fluorescence tests. The results show that amoxicillin effectively inhibited Escherichia coli and Staphylococcus aureus -resistant bacteria in the presence of 4-Cpba. The in vivo experimental results show that the CPA NPs exhibited a synergistic anti-infective effect in vivo , which inhibited the inflammatory response and apoptosis induced by the drug-resistant bacterial infection, and promoted wound healing in mice. The hematoxylin and eosin staining and blood biochemical experiments revealed that the acute toxicity of the material was negligible and it had good biocompatibility. Our results verify our design that CPA NPs can restore the antibacterial activity of amoxicillin.