NU 2016-031

INVENTORS

Andrew Lee

Marc Scheetz

Alan Hauser*

Nathaniel Rhodes

SHORT DESCRIPTION

Modified nanoparticles that bind and/or kill bacteria

BACKGROUND

The emergence of bacterial pathogens resistant to many or all conventional antibiotics is a crisis in healthcare. Since current economic models have dissuaded pharmaceutical companies from developing new antibiotics, it is likely that this problem will only worsen in the coming years. It is therefore critical that novel means to enhance the efficacy of currently available antibiotics be explored.  Several groups sought to design antibiotic-conjugated nanoparticle to target bacteria.  However, optimization of conjugation and choice of antibiotic and use of synergistic antibiotics have fallen short in effectively treating infection.

ABSTRACT

Northwestern researchers have designed nanoparticle scaffold platform that is decorating with peptidoglycan-binding antibiotics, making them optimized to bind Gram-positive pathogens..  The conjugation of nanoparticles with the antibiotic polymyxin B, for example, increases the antibiotic efficacy due to increased lipopolysaccharide binding of gram-negative bacteria and higher favorable pharmacokinetic/ pharmacodynamic properties compared to conventionally administered antibiotics alone.  The polymyxin B nanoparticle platform facilitates the concentration of antibiotics at sites of infection, limiting exposure elsewhere within the host and minimizing adverse effects of antibiotics on host tissues.  It enables the delivery of spatially concentrated boluses of polymyxin B itself to bacteria as well as delivery vehicles for other antibiotics. The platform allows for the addition of a second synergistic antibiotic, such as vancomycin (V) as well.  The co-localization of two different antibiotics offers an optimal configuration on the surface of the nanoparticle, enhancing and maximizing the bactericidal efficacy beyond that achieved by intravenous administration of free antibiotics.  The dual action potently attacks two essential structures simultaneously, minimizing antibiotic resistance.

APPLICATIONS

• Treatment of infections caused by gram-negative bacteria, including multidrug-resistant bacteria

ADVANTAGES

• Optimized targeting of nanoparticle-polymyxin B complexes to bacteria
• Delivery of two or more synergistic antibiotics at high localized concentrations to a single bacterium
• Favorable pharmacokinetic/pharmacodynamic properties related to nanoparticle complex structure than antibiotics alone

IP STATUS

A US patent application has been filed.