Delivery of antibiotics coupled to iron oxide nanoparticles across the biofilm of mucoid Pseudonomas aeruginosa and investigation of their efficacy

摘要

Pseudomonas aeruginosa bacterium is a deadly pathogen, leading to respiratory failure in cystic fibrosis and nosocomial pneumonia, and responsible for high mortality rates in these diseases. P. aeruginosa has inherent as well as acquired resistance to many drug classes. In this paper, we investigate the effectiveness of two classes; aminoglycoside (tobramycin) and fluoroquinolone (ciprofloxacin) administered alone, as well as conjugated to iron oxide (magnetite) nanoparticles. P. aeruginosa possesses the ability to quickly alter its genetics to impart resistance to the presence of new, unrecognized treatments. As a response to this impending public health threat, we have synthesized and characterized magnetite nanoparticles capped with biodegradable short-chain carboxylic acid derivatives conjugated to common antibiotic drugs. The functionalized nanoparticles may carry the drug past the mucus and biofilm layers to target the bacterial colonies via magnetic gradient-guided transport. Additionally, the magnetic ferrofluid may be used under application of an oscillating magnetic field to raise the local temperature, causing biofilm disruption, slowed growth, and mechanical disruption. These abilities of the ferrofluid would also treat multi-drug resistant strains, which appear to be increasing in many nosocomial as well as acquired opportunistic infections. In this in vitro model, we show that the iron oxide alone can also inhibit bacterial growth and biofilm formation.