The antimicrobial efficacy of sustained release silver-carbene complex-loaded L-tyrosine polyphosphate nanoparticles: characterization, in vitro and in vivo studies.
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.
Hindi
Khadijah M
KM
Department of Chemistry, University of Akron, Akron, OH 44325-3601, USA.
Ditto
Andrew J
AJ
Panzner
Matthew J
MJ
Medvetz
Douglas A
DA
Han
Daniel S
DS
Hovis
Christine E
CE
Hilliard
Julia K
JK
Taylor
Jane B
JB
Yun
Yang H
YH
Cannon
Carolyn L
CL
Youngs
Wiley J
WJ
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
D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D010755:Organophosphates; D011108:Polymers; C542009:tyrosine polyphosphate; C030011:carbene; D012834:Silver; D008697:Methane