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...

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Bibliographic Details
Published in:Biomaterials 2009-08, Vol.30 (22), p.3771-3779
Main Authors: Hindi, Khadijah M, Ditto, Andrew J, Panzner, Matthew J, Medvetz, Douglas A, Han, Daniel S, Hovis, Christine E, Hilliard, Julia K, Taylor, Jane B, Yun, Yang H, Cannon, Carolyn L, Youngs, Wiley J
Format: Article
Language:English
Subjects:
Administration, Inhalation
Advanced Basic Science
Animals
Anti-Infective Agents - administration & dosage
Anti-Infective Agents - therapeutic use
Antimicrobial
Biocompatible Materials - chemistry
Biocompatible Materials - metabolism
Controlled drug release
Cystic fibrosis
Cystic Fibrosis - drug therapy
Cystic Fibrosis - microbiology
Dentistry
Drug Resistance, Multiple, Bacterial - drug effects
Humans
Male
Materials Testing
Methane - analogs & derivatives
Methane - chemistry
Methane - pharmacology
Methane - therapeutic use
Mice
Mice, Inbred C57BL
Microbial Sensitivity Tests
Molecular Structure
Nanoparticle
Nanoparticles - chemistry
Nanoparticles - therapeutic use
Nebulizers and Vaporizers
Organophosphates - chemistry
Organophosphates - metabolism
Particle Size
Polymers - chemistry
Polymers - metabolism
Pseudomonas aeruginosa
Pseudomonas aeruginosa - drug effects
Respiratory Tract Infections - drug therapy
Respiratory Tract Infections - microbiology
Silver
Silver - chemistry
Silver - pharmacology
Silver - therapeutic use
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Summary: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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2009.03.044