THE UNIVERSITY OF AKRON
This supplement will accelerate the progress of the four aims of the parent grant by adding a postdoctoral research associate, who is a leading expert in the synthesis and study of silver carbene complexes (SCCs), to the investigative team. Further a Nuclear Magnetic Resonance (NMR) expert and his laboratory will be added to characterize the structure and purity of new SCC's, polymers that will be used for the preparation of nanoparticles and compositions of SCC-nanoparticle complexes; adding an expert in Polymer synthesis and her laboratory to greatly enhance the team's abilities to design the SCC's and nanoparticles with controlled loadings and release rates in order to keep the dosage of antimicrobial above the MIC level for a period of time sufficient to kill the biofilm. Further, nanoparticles will be loaded with DNAse to help degrade the biofilm structure; adding a postdoctral research associate to conduct in vivo studies using a mouse inhalation tower and jet nebulizer that will allow precise dosing of multiple animals simultaneously with minimal loss of drug in the device itself. This delivery method most closely emulates treatment of ambulatory patients, our largest target population. Further, a used Zeiss confocal microscope will be purchased to enhance viewing of biofilms; adding an expert in numerical simulations of depostion problems to develop and solve models for the transport of nanoparticles through the lung and their deposition onto biofilms in the respiratory tract. These models will be integrated with the parent grant to form a comprehensive model of the lung-biofilm system.