Nitric oxide-releasing dendrimers for the treatment of periodontal disease

 描述(申请人提供)：这项建议的目标是开发一氧化氮释放树枝状大分子，以抑制基于生物膜的牙周病原体和相关的牙周疾病。进行这项工作的基本原理是基于一氧化氮的广谱抗菌活性、在生物膜中的快速扩散、较短的半衰期(从而赋予局部Acton)以及在对病原体的免疫反应中的生理作用。大分子NO释放支架的使用使我们能够最大限度地发挥杀菌活性，同时将对健康口腔细胞和组织的细胞毒性影响降至最低。我们将研究树枝状大小/分子质量、电荷、外部官能度和NO释放特性对致病菌斑细菌杀灭的影响。我们将系统地研究树枝状分子和一氧化氮对口腔菌斑生物膜体外模型的渗透，作为生物膜组成、成熟度和质量的函数。已建立的小鼠牙周感染模型将用于评估树突状分子组成和一氧化氮释放如何影响炎症、宿主免疫反应和生物膜根除。

 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.