Nitric oxide-releasing dendrimers for the treatment of periodontal disease

用于治疗牙周病的释放一氧化氮的树枝状聚合物

基本信息

批准号：
9261511
负责人：
Mark H Schoenfisch
金额：
$ 30.99万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-02 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9261511
关键词：
Adult Adverse effects Aerobic Anaerobic Bacteria Anti-Bacterial Agents Anti-Inflammatory Agents Anti-inflammatory Antibiotics Awareness Bacteria Caliber Cardiovascular Diseases Caring Cells Characteristics Charge Chemicals Cystic Fibrosis Dendrimers Dental Care Dental Plaque Diabetic Foot Ulcer Diffusion Epidemic Expenditure Foreign Bodies Generations Gingiva Gingivitis Goals Half-Life Health Health Expenditures Healthcare Systems Heart Diseases Immune response In Vitro Infection Inflammation Innate Immune Response Kinetics Local Anti-Infective Agents Malignant Neoplasms Microbial Biofilms Microbiology Modeling Molecular Weight Mus Nature Nitric Oxide Oral Oral health Pathogenicity Penetration Periodontal Diseases Periodontal Infection Periodontal Pocket Periodontitis Physiological Prevention Property Research Risk Factors Role Safety Stroke Structure System Testing Tissues Work antimicrobial bactericide base combat cytotoxic cytotoxicity design efficacy study in vitro Model in vivo killings lipophilicity microbial microbial community molecular size mouse model novel strategies oral plaque pathogen periodontopathogen prevent programs public health relevance response scaffold soft tissue subcutaneous subgingival biofilm success therapeutic development

项目摘要

DESCRIPTION (provided by applicant): The goal of this proposal is to develop nitric oxide releasing dendrimers to inhibit biofilm based periodontopathogens and associated periodontal disease. The rationale for pursuing this work is based on nitric oxide's broad spectrum antimicrobial activity, rapid diffusion through biofilms, short half-life (thus imparting local acton) and physiological role in the immune response to pathogens. The use of a macromolecular NO release scaffold enables us to maximize bactericidal activity while minimizing the cytotoxic impact on healthy oral cells and tissue. We will study the influence of dendrimer size/molecular weight, charge, exterior functionality, and NO release properties on pathogenic plaque bacteria killing. We will systematically study both dendrimer and nitric oxide penetration into in vitro models of oral plaque biofilms as a function of biofilm composition, maturity and mass. An established murine model for periodontal infection will be employed to evaluate how dendrimer composition and nitric oxide release influence inflammation, host immune response, and biofilm eradication.

描述（由申请人提供）：本提案的目标是开发一氧化氮释放树枝状聚合物，以抑制基于生物膜的牙周病原体和相关牙周病。开展这项工作的基本原理是基于一氧化氮的广谱抗菌活性、通过生物膜的快速扩散、大分子NO释放支架的半衰期短（从而赋予局部作用）和在病原体免疫反应中的生理作用。最大限度地提高杀菌活性，同时最大限度地减少对健康口腔细胞和组织的细胞毒性影响。我们将研究树枝状聚合物的大小/分子量、电荷、外部功能和一氧化氮释放特性对致病菌斑细菌杀灭的影响。一氧化氮渗透到口腔菌斑生物膜的体外模型中，作为生物膜组成、成熟度和质量的函数，将采用已建立的牙周感染小鼠模型来评估树枝状聚合物组成和一氧化氮的关系。氧化物释放影响炎症、宿主免疫反应和生物膜根除。