title: The antimicrobial efficacy of sustained release silver-carbene complex-loaded L-tyrosine polyphosphate nanoparticles: characterization, in vitro and in vivo studies.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH 44325-3601, USA.
authors.forename: Khadijah M
authors.initials: KM
authors.lastname: Hindi
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ditto
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Panzner
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Medvetz
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Han
authors.forename: Christine E
authors.initials: CE
authors.lastname: Hovis
authors.forename: Julia K
authors.initials: JK
authors.lastname: Hilliard
authors.forename: Jane B
authors.initials: JB
authors.lastname: Taylor
authors.forename: Yang H
authors.initials: YH
authors.lastname: Yun
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Cannon
authors.forename: Wiley J
authors.initials: WJ
authors.lastname: Youngs
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D006801:Humans; D008297:Male; D008422:Materials Testing; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009330:Nebulizers and Vaporizers; D010755:Organophosphates / Q000737:chemistry / Q000378:metabolism; D010316:Particle Size; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D012834:Silver / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D010755:Organophosphates; D011108:Polymers; C542009:tyrosine polyphosphate; C030011:carbene; D012834:Silver; D008697:Methane