Chitosan-Nanoparticle Enhanced Antibiotic and ?-Lactamase Inhibitor to Treat Multi-Drug Resistant Pathogens

Antibiotic resistant bacteria (ARBs) are responsible for at least 2,868,700 infections and 35,900 deaths annually in the United States. Among ARBs, one type that causes serious threats to public health is extended-spectrum b-lactamase (ESBL)-producing Enterobacteriaceae, which mediates the resistance to most b-lactamase antibiotics (e.g penicillins) and undermines the efficacy of current antibiotic therapies. Thus, it is critical to make antibiotics effective again through low-cost and high-effective nano-antibiotics or alternative antimicrobials. In this study, we develop an innovative antimicrobial therapy against multi-drug resistant bacteria by engineered chitosan nanoparticle coated β-lactam antibiotic and β-lactamase inhibitors (CNAI) using a water-oil-water (w/o/w) emulsion method. The w/o/w ensures the high-effective encapsulation of chitosan nanoparticles on the antibiotic and inhibitors and a slow and controllable drug release via a core-shell nanostructure. The chitosan nanoparticles with antibiotics/inhibitors (CNAI) were evaluated for their physicochemical properties, antimicrobial activity, and the drug loading behaviors. The results show that all combinations of CNAI have a particle size of around 200 nm, a Minimum Inhibitory Concentration (MIC) of 1 ug/ml and are effective at inhibiting multi-drug resistant bacteria. The chitosan nanoparticles engaged in the system are expected to enhance antibacterial properties and provide controllable release function to increase the entire antibiotic efficiency.