A novel therapy for advanced periodontitis

晚期牙周炎的新疗法

• 批准号: 6922946
• 负责人: Edward J Boland
• 金额: $ 16.64万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6922946
• 关键词: biodegradable product; bioengineering /biomedical engineering; biomaterial compatibility; blood chemistry; cytotoxicity; dental disorder chemotherapy; dental implants; drug adverse effect; drug delivery systems; drug design /synthesis /production; drug screening /evaluation; laboratory rat; medical implant science; neurotoxins; nonhuman therapy evaluation; periodontitis; phenothiazines; preventive dentistry; slow release drug; therapy design /development

DESCRIPTION: Periodontitis is the most prevalent form of bone pathology in the United States with 15-25% of all individuals suffering from moderate to severe forms. The progression of the disease, if untreated, leads to bone resorption and the eventual loss of the tooth. The objectives of this project are to bioengineer a novel, effective and low-maintenance therapy for periodontal disease which eliminates the bone resorption and tooth loss. This will be accomplished through the use of the (+) enantiomer of promethazine HCI or a hydrophilic analog Of (+) PMZ delivered through an implantable, control release device which maintains plasma levels of drug within the effective, bone loss preventing range for two to four weeks. To accomplish this goal, we proposed to 1) synthesize a biodegradable, controlled released (+) PMZ device. This device will be engineered to for zero order release kinetics over two months and will be implantable subdermally or in the oral cavity. 2) Determine the toxicity and release kinetics of the implant in a rat model. Release kinetics will be established by implanting the (+) PMZ device in rats and analyzing blood samples, drawn daily, for plasma (+) PMZ concentration. Toxicity will be determined at the end of the two week period by histologic examination of the tissues surrounding the implant site and from the liver, kidney, spleen and brain. 3) Determine the in vivo efficacy of the (+) PMZ device using a rat model for periodontal disease. (+) PMZ devices will be implanted as above. The upper left 1st molar of the rat will be ligated with surgical suture to induce periodontitis. Bone loss in the affected area will be determined and compared to that of untreated animals. 4) Synthesize and characterize a hydrophilic analog of (+) PMZ. (+) PMZ will be chemically altered by the addition of hydrophilic moieties at appropriate sites within the parent molecule. Cytotoxicity and efficacy of the analog will be determined in vitro and in vivo. The result of this project will be the preliminary development of a safe, effective and low maintenance treatment for periodontitis which will prevent tooth loss in affected patients.

描述：牙周炎是美国最常见的骨病理形式，15-25% 的人患有中度至重度牙周炎。如果不治疗，疾病的进展会导致骨吸收并最终导致牙齿脱落。该项目的目标是通过生物工程设计一种新颖、有效且低维护的牙周病疗法，消除骨吸收和牙齿脱落。这将通过使用盐酸异丙嗪的 (+) 对映体或 (+) PMZ 的亲水性类似物通过可植入的控制释放装置输送来实现，该装置将药物的血浆水平维持在有效的、预防骨质流失的范围内，持续两至四个星期。为了实现这一目标，我们建议 1) 合成可生物降解、受控释放 (+) PMZ 装置。该装置将被设计为在两个月内实现零级释放动力学，并将可植入皮下或口腔中。 2) 确定植入物在大鼠模型中的毒性和释放动力学。将通过将 (+) PMZ 装置植入大鼠体内并分析每天抽取的血液样本的血浆 (+) PMZ 浓度来建立释放动力学。两周后，将通过对植入部位周围的组织以及肝脏、肾脏、脾脏和大脑进行组织学检查来确定毒性。 3) 使用牙周病大鼠模型确定 (+) PMZ 装置的体内功效。 (+) PMZ 设备将按上述方式植入。将大鼠的左上第一磨牙用手术缝合线结扎以诱发牙周炎。将确定受影响区域的骨质流失，并与未经治疗的动物进行比较。 4) 合成并表征 (+) PMZ 的亲水类似物。 (+) PMZ 将通过在母体分子内的适当位点添加亲水部分而发生化学改变。类似物的细胞毒性和功效将在体外和体内测定。该项目的结果将是初步开发出一种安全、有效且维护费用低的牙周炎治疗方法，以防止受影响患者的牙齿脱落。