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

描述（由申请人提供）：本申请旨在开发一种治疗性药物偶联物，目的是为减少成人牙周炎患者的牙袋深度提供一种具有成本效益的辅助方法。这项拟议的研究属于现有的项目公告（PA-06-085），重点是“开发用于快速和/或持续按需释放口腔治疗剂（例如，抗菌剂，抗炎剂，抗体，肽，核苷酸，小分子受体激动剂/拮抗剂）的新型递送系统”。为此，本申请的目的将是制定和测试几种现有治疗剂的新衍生物的能力，这些药物在早期测试中已被证明对中性粒细胞衍生的蛋白酶有效，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)测试配方抑制与牙周病相关的兼性厌氧菌的有效性；2)测试其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牙周病中起主要作用。这种创新和合理的设计源于这样一个想法，即在牙周袋环境中处理多个生物分子目标应该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，调节一系列蛋白酶并解决细菌负担是临床研究的主题。公共卫生意义：牙周病是世界上最常见的慢性传染病。在以口腔健康著称的美国，50%以上的成年人患有牙龈炎，35%患有牙周炎。在美国，牙病对社会和经济都有重大影响，据估计，每年有1.89亿小时的工作时间被遗漏，与牙病相关的费用超过600亿美元。越来越多的证据表明，牙齿和牙周病会导致其他代价高昂的全身性疾病，如心血管、肺部、消化道和肝脏疾病、早产和糖尿病，如果考虑到这一点，成本就会高得多。

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.