Dual stimuli-responsive silver loaded
nanoparticles eliminate bacterial biofilms
Overview
Bacterial biofilms are complex, 3D bacterial communities that are embedded in a self-produced matrix of extracellular polymeric substances. Although biofilms are a common occurrence in human infections, they are extremely difficult to eradicate as their matrix acts as a barrier that prevents the infiltration of antibiotics and other antimicrobial agents. Because of this, biofilm infections are a significant challenge for physicians to treat, often become chronic, and can lead to the development of antibiotic resistance. In this way, there is an urgent need for advanced therapeutics that can penetrate the biofilm matrix, deliver potent antibiotics, and thus more effectively eradicate biofilm infections. The disclosed technology presents such a novel therapy through the engineering of dual stimuli-responsive nanoparticles. In this way, the engineered nanoparticles respond to pH and enzymes within the biofilm to locally deliver antibiofilm (nuclease) and antibacterial agents (silver nanoparticles) in order to improve the treatment of biofilm infections.
Market Opportunity
Biofilm-associated bacterial infections are considered one of the greatest threats to health worldwide. It is estimated that around 17 million new biofilm-associated infections arise and lead to up to 550,000 deaths annually in the United States alone. Biofilms are involved in various conditions including dental caries, urinary tract infections, burn wound infections and diabetic foot ulcers. Currently, the gold standard for treatment of biofilm-related infections is oral or intravenous administration of United States Food and Drug Administration (FDA) approved antibiotics. However, high antibiotic doses (up to 10-1000 times greater than concentrations effective against planktonic bacteria) and prolonged treatment times are usually required for the treatment of biofilm-associated bacterial infections, which can exacerbate toxicity, have poor penetration and contribute to antibiotic resistance. The disclosed technology features sophisticated engineering to generate responsive nanoparticles that are better able to penetrate biofilms, deliver therapeutic agents locally and dynamically respond to the environment of the biofilm.
Innovation and Meaningful Advantages
Nanoparticles (NPs) are promising drug-delivery vehicles for the targeted therapy of biofilms. The present technology is built upon an advanced and holistic understanding of the environment surrounding biofilm development and maturation. A gelatin nanoparticle is utilized, with its formulation able to effectively disrupt the biofilm matrix itself, as gelatinases (i.e. enzymes that are capable of degrading gelatin) are produced by common biofilm pathogens. This ensures that the NP is degraded and thus delivers its therapeutic load directly at infection sites. Further, the developed NPs contain nuclease which degrade extracellular DNA, a major component of biofilms, and silver nanoparticles that act as a broad-spectrum antibiotic. In order to protect this therapeutic load further, a pH degradable coating of the NPs is employed, which protects the antibiofilm (nuclease) and antibacterial agents (silver nanoparticles) until the NP reaches the low pH environment of the biofilm. The preclinical work surrounding this technology is extremely promising, with S. aureus and S. epidermidis biofilm biomass decreasing upon treatment with increasing concentrations of the NPs.
Collaboration Opportunity
We are interested in exploring research collaborations and licensing opportunities
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