The antimicrobial efficacy of sustained release silver–carbene complex-loaded l-tyrosine polyphosphate nanoparticles

Khadijah M. Hindi^a, Andrew J. Ditto^b, Matthew J. Panzner^a, Douglas A. Medvetz^a, Daniel S. Han^c, Christine E. Hovis^c, Julia K. Hilliard^c, Jane B. Taylor^c, Yang H. Yun^{b, ,} , Carolyn L. Cannon^{c, ,} and Wiley J. Youngs^{a, ,}

^aDepartment of Chemistry, University of Akron, Akron, OH 44325-3601, USA

^bDepartment of Biomedical Engineering, University of Akron, Akron, OH 44325-0302, USA

^cDepartment of Pediatrics, Washington University School of Medicine, St. Louis, MI 63110-1002, USA

Received 19 January 2009;

accepted 17 March 2009.

Available online 23 April 2009.

The pressing need to treat multi-drug resistant bacteria in the chronically infected lungs of cystic fibrosis (CF) patients has given rise to novel nebulized antimicrobials. We have synthesized a silver–carbene complex (SCC10) active against a variety of bacterial strains associated with CF and chronic lung infections. Our studies have demonstrated that SCC10-loaded into l-tyrosine polyphosphate nanoparticles (LTP NPs) exhibits excellent antimicrobial activity in vitro and in vivo against the CF relevant bacteria Pseudomonas aeruginosa. Encapsulation of SCC10 in LTP NPs provides sustained release of the antimicrobial over the course of several days translating into efficacious results in vivo with only two administered doses over a 72 h period.



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