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Cationic CAMKIIN nanoparticles that reduce chlorine-induced airway oxidative stress

阳离子 CAMKIIN 纳米颗粒可减少氯诱导的气道氧化应激

基本信息

批准号：
10408405
负责人：
Aliasger K Salem
金额：
$ 19.31万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-06 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10408405
关键词：
Acute Adolescent Adverse effects Animals Biological Assay Biological Availability Body Weight Changes Budesonide Cations Cells Cessation of life Chemical Agents Chemicals Chemistry Chitosan Chlorine Data Dose Drug Delivery Systems Encapsulated Epithelial Cells FDA approved Fibrosis Future Generations Glycolates Goals Hepatotoxicity Human Inflammation Inhalation Inhalation Exposure Link Lung Mitochondria Modality Modeling Mus Oropharyngeal Oxidative Stress Peptides Pharmaceutical Preparations Play Production Protein Isoforms Pulmonary Inflammation RNA Reactive Oxygen Species Reporting Research Reverse Transcriptase Polymerase Chain Reaction Role Rolipram Surface System Technology Testing Therapeutic Therapeutic Agents Therapeutic Effect Time Water airway epithelium airway hyperresponsiveness airway inflammation airway remodeling base biodegradable polymer calmodulin-dependent protein kinase II chlorine gas cytokine experimental group high reward high risk improved inhibitor innovation lipophilicity local drug delivery lung histology lung injury magnetic beads methacholine nanoparticle nanoparticle delivery new therapeutic target novel strategies novel therapeutics preclinical study pulmonary function residence respiratory health response uptake

项目摘要

Project Summary Chlorine is a chemical agent that is harmful to humans. Acute inhalation of high levels of chlorine results in the death of airway epithelial cells and leads to adverse effects on respiratory health, including airway remodeling and hyperreactivity. In a mouse chlorine exposure model, animals developed inflammation and fibrosis in large airways. This inflammation and fibrosis has been reported to be linked to damage to mitochondria and the generation of oxidative stress and reactive oxygen species. Our group has shown that Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a pivotal role in ROS generation in the airways. In this proposal, we will test the hypothesis that, in response to chlorine gas challenge, CaMKII contributes to the induction of hallmark features of airway inflammation. Utilizing a novel drug delivery system, we will expose mice to a CaMKII inhibitor peptide (CaMKIIN) encapsulated in PLGA NPs. These NPs will be directly delivered to the lung via oropharyngeal instillation. Furthermore, we will include a chitosan coating of the CaMKIIN-loaded PLGA-NPs to increase uptake in lung cells thereby reducing oxidative stress and fibrosis. This project will be completed by first evaluating CaMKII activation and ROS expression levels in the lungs of juvenile mice following chlorine exposure and then determining if a CaMKII inhibitor-loaded cationic nanoparticle can mitigate ROS expression and lung damage following chlorine exposure.

项目总结