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Silver carbene complexes as treatment of CF lung disease

银卡宾配合物治疗 CF 肺病

基本信息

批准号：
7410085
负责人：
Carolyn Louise Cannon
金额：
$ 35.71万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-01 至 2010-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7410085
关键词：
Acceleration Address Agar Animals Antibiotic Resistance Burkholderia cepacia complex Burn injury Cations Chronic Clinical Complex Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Deterioration Dose Drug Delivery Systems Drug Metabolic Detoxication Epidemic Epithelial Cells Goals In Vitro Infection Infection Control Laboratories Ligands Lung Microarray Analysis Modeling Multi-Drug Resistance Mus Organism Outpatients Pathogenesis Patients Predisposition Property Pseudomonas aeruginosa Pulmonary Cystic Fibrosis Recording of previous events Research Personnel Resistance Silver Silver Compounds Solubility Solvents Staphylococcus aureus Structure of respiratory epithelium Testing Therapeutic Topical application Toxic effect Tracheal Epithelium Water antimicrobial antimicrobial drug base carbene cystic fibrosis patients disilver oxide improved in vivo novel pathogen physical property response

项目摘要

The long-term goal of these studies is to explore the utility of silver carbene complexes as antimicrobial agents in the treatment of pulmonary infections with emphasis on treatment of the chronic infections of the cystic fibrosis (CF) lung. Silver N-heterocyclic carbene complexes have antimicrobial activity against all bacterial species tested to date including the CF lung pathogens Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) organisms. The silver carbene complexes are water soluble, and hence amenable to nebulization for drug delivery. Silver complexes have a long history of safe use for topical applications, however, the use of silver compounds to treat pulmonary infections has not been explored. In addition to in vitro and in vivo toxicity studies aimed at determining the effects of silver complexes on the respiratory epithelium, we will establish the efficacy of these compounds for treatment of the primary CF pathogen P. aeruginosa, as well as the less common Bcc organisms, particularly B. dolosa, the causative agent of a recent epidemic. The B. dolosa strains are the most antibiotic resistant among the Bcc organisms. Virtually nothing is known about the pathogenesis of the lung infections caused by B. dolosa, and no effective therapy currently exists for these patients. We aim to characterize a novel murine model of 8. dolosa infection and use this model, as well as more established models of P. aeruginosa lung infections, to test the in vivo properties of these newly developed silver-based antimicrobial agents. Specifically, we aim to 1) synthesize silver carbene complexes as candidate antimicrobial agents; 2) determine the antimicrobial properties and toxicity profiles of the silver carbene compounds with the most promising physical properties, as well as the mechanisms of epithelial cell-silver toxicity or detoxification; and 3) develop murine models of chronic pulmonary infection with resistant CF pathogens and use these models to determine the in vivo efficacy of the leading silver carbene compounds for treatment of pulmonary infections.

这些研究的长期目标是探索卡宾银配合物作为抗菌药物的用途

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Aerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexes.

DOI：
10.1021/mp3004379
发表时间：
2012-11-05
期刊：
Molecular pharmaceutics
影响因子：
4.9
作者：
Ornelas-Megiatto C;Shah PN;Wich PR;Cohen JL;Tagaev JA;Smolen JA;Wright BD;Panzner MJ;Youngs WJ;Fréchet JM;Cannon CL
通讯作者：
Cannon CL

The medicinal applications of imidazolium carbene-metal complexes.

DOI：
10.1021/cr800500u
发表时间：
2009-08
期刊：
CHEMICAL REVIEWS
影响因子：
62.1
作者：
Hindi, Khadijah M.;Panzner, Matthew J.;Tessier, Claire A.;Cannon, Carolyn L.;Youngs, Wiley J.
通讯作者：
Youngs, Wiley J.