A Novel & Tailorable Drug Delivery Device for the Treatment of Periodontitis

描述（由申请人提供）：本申请涉及治疗药物缀合物的开发，其目的是提供一种用于减少成人牙周炎患者牙周袋深度的洁治和根面平整程序的成本有效的辅助物。这项拟议的研究福尔斯属于现有的计划公告（PA-06-085），重点是“开发用于快速和/或持续、按需释放治疗剂（例如，抗微生物剂、抗炎剂、抗体、肽、核苷酸、小分子受体激动剂/拮抗剂）”。为此，本申请的目的将是配制和测试现有治疗剂的几种新型衍生物的能力，所述现有治疗剂在早期测试中已被证明对嗜酸性粒细胞衍生的蛋白酶、对几种已知的牙周病原体和蛋白酶有效。这项工作的主要具体目的是：1）测试制剂抑制与牙周病相关的兼性厌氧菌的有效性; 2）测试它们抑制细菌和宿主来源的蛋白酶活性的有效性，这些蛋白酶被认为在这种疾病中发挥着重要作用。这种创新和合理的设计源于这样一种想法，即在牙周袋环境中解决多个生物分子靶点应该会导致更有利的愈合环境。因此，开发一种可生物降解的、具有成本效益的基于微球的牙周炎治疗方法是临床研究的主题，该方法可调节一系列蛋白酶并解决细菌负荷。公共卫生意义：牙周病是世界上最常见的慢性传染病。在美国，中国是一个以良好的口腔保健而闻名的国家，超过50%的成年人患有牙龈炎，35%的人患有牙周炎。牙科疾病在美国具有重大的社会和经济影响，估计每年造成1.89亿小时的工作时间和超过600亿美元的疾病费用。当越来越多的证据表明，牙齿和牙周病有助于其他昂贵的系统性疾病，如心血管，肺，消化和肝脏疾病，早产和糖尿病的考虑，成本显着更高。

DESCRIPTION (provided by applicant): This application is directed toward the development of a therapeutic drug conjugates with the intention of providing a cost effective adjunct to scaling and root planing procedures for the reduction of pocket depth in patients with adult periodontitis. This proposed study falls under an existing program announcement (PA-06-085) focusing on the "development of novel delivery systems for rapid and/or sustained, on-demand release of therapeutic agents (e.g., antimicrobial, anti-inflammatory, antibodies, peptides, nucleotides, small molecule receptor agonists/antagonists) in the oral cavity". To this end, the objective of this application will be to formulate and test the ability of several novel derivatives of an existing therapeutic agent that has proven to be effective against neutrophil-derived proteases in early testing, against several known periodontal pathogens and proteases. The major Specific Aims of this work are: 1) to test the effectiveness of the formulations to inhibit facultative anaerobes associated with periodontal disease and 2) to test their effectiveness in inhibiting the activities of bacterial and host-derived proteases that are believed to play major roles in this disease. This innovative and rational design resulted from the idea that addressing multiple biomolecular targets within the periodontal pocket environment should result in a more favorable environment for healing. Thus, the development of a biodegradable, cost-effective microsphere-based treatment for periodontitis that modulates an array of proteases and addresses bacterial burden is the subject of a clinical investigation. Public Health Significance: Periodontal disease is the most common chronic infectious disease in the world. In the U.S., a country known for good oral healthcare, more than 50 percent of adults have gingivitis and 35 percent have periodontitis. Dental disease has both a significant social and economic impact in the U.S. and is estimated to cause 189 million missed hours of work each year and expenses attributed to the disease of more than $60 billion. When the growing evidence that tooth and periodontal disease contributes to other costly systemic diseases such as cardiovascular, pulmonary, digestive and liver diseases, and preterm births, and diabetes are considered, the costs are significantly higher.