Rechargeable Infection-responsive Anticandidal Denture Materials

可充电感染反应型抗念珠菌义齿材料

• 批准号: 8597913
• 负责人: CHIH-KO YEH
• 金额: --
• 依托单位: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-10-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8597913
• 关键词: Affect; Animal Model; Antifungal Agents; Appearance; Azoles; Binding; Biochemical; Candida; Catheters; Cessation of life; Charge; Chemicals; Chlorhexidine; Clinical; Clinical Trials; Coculture Techniques; Dental Care; Dental Infection Control; Dental caries; Denture Bases; Denture Stomatitis; Denture Wear; Dentures; Devices; Disease; Disinfection; Drug Controls; Drug Delivery Systems; Edetic Acid; Elderly; Environment; Epithelium; Evaluation; Future; General Population; General Practices; Glass Ionomer Cements; Goals; Habits; Health; Healthcare; Human; Hydrogen Bonding; Hygiene; In Vitro; Incidence; Individual; Infection; Intake; Kinetics; Lead; Link; Mechanics; Medical; Medical Device; Miconazole; Microbial Biofilms; Modeling; Mouth Diseases; Natural regeneration; Nutritional; Nystatin; Oral; Oral health; Patients; Periodontal Diseases; Personal Satisfaction; Pharmaceutical Preparations; Pilot Projects; Plant Resins; Polyenes; Population; Prevention; Property; Prosthesis; Quality of life; Reagent; Recurrence; Research; Resistance; Risk; Risk Factors; Rotation; Safety; Salivary; Solubility; Speech; Structure; System; Systemic disease; Systemic infection; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Tooth Diseases; Tooth Loss; Tube; Urethane; Veterans; Water; antimicrobial; base; biomaterial compatibility; effective therapy; endotracheal; fighting; gastrointestinal; gluconate; histatin 5; innovation; methacrylic acid; microbial; microorganism; monomer; new technology; novel strategies; oral cavity epithelium; oral infection; polypeptide; prevent; public health relevance; reconstitution; treatment strategy; van der Waals force

DESCRIPTION (provided by applicant): Candida-associated denture stomatitis (CADS) is a common, recurring disease among denture wearers and can lead to other oral health problems, systemic infections, compromised quality of life, and even death. Thus far, there are no effective treatment strategies to control CADS, particularly for the elderly veteran population who are often immunologically and/or medically compromised. This project will develop a rechargeable, "click-on/click-off" anticandidal technology to manage CADS. We propose that methacrylic acid (MAA) moieties can be incorporated into denture materials and act as a "rechargeable battery" to bind and then slowly release antifungal drugs. Our preliminary studies have demonstrated that MAA (up to 10%) can be copolymerized with denture resin monomers in the curing step without negatively affecting the physical/mechanical properties of the resulting resins. Antifungal drugs such as miconazole and chlorhexidine digluconate can be charged into the new denture materials and slowly released for a prolonged period of time (weeks or months). The drugs could be "quenched" (washed out or "clicked" off) by treating the denture materials with a quenching agent such as EDTA, and the quenched denture materials can be recharged with the same or different antifungal reagents. In the current proposal, we will test the hypothesis that this technique can be applied to both urethane-based and acrylic-based denture materials with three anticandidal drugs of different chemical and biochemical structures, i.e., a azole (miconazole), a polyene (nystatin) and a salivary antimicrobial polypeptide (synthetic histatin 5). The specific aims of the proposed research are to: (1) fabricate new acrylic and urethane rechargeable anticandidal denture materials, and characterize the physical/mechanical properties of the new materials, (2) formulate the anticandidal drug-containing denture materials, establish drug binding/releasing kinetics, and evaluate the "click-on/click-off" anticandidal technology of the new denture materials, and (3) evaluate in vitro the biocompatibility and anticandidal activity of the new denture materials and the risk of microbial resistance to the materials. The evaluation of biocompatibility and anticandidal efficacy of the new systems will be performed in vitro with human oral epithelium-Candida and reconstituted human epithelium (RHE)-Candida co-culture models. The potential risk of developing microbial resistance will also be tested to determine the safety of the new approach. The rechargeable, "click-on/click-off" anticandidal denture materials developed in this project can activate and terminate antifungal drug treatment depending on the presence or absence of clinical Candida infection. The rechargeable feature will likely allow switching to more potent/effective reagents to enhance anticandidal potency and/or minimize the risk of fungal resistance, leading to a personalized therapeutic strategy for CADS and other related diseases. Furthermore, this new technology could be potentially used in a broad range of drug delivery systems for other oral or systemic diseases and/or infection control of dental/medical devices.

描述（由申请人提供）： 与念珠菌相关的义齿口腔炎（CADS）是牙齿佩戴者中常见的疾病，可能导致其他口腔健康问题，全身感染，生活质量造成的质量甚至死亡。到目前为止，还没有有效的治疗策略来控制CAD，特别是对于经常在免疫学和/或医学上受到损害的老年退伍军人人口而言。该项目将开发一种可充电的“单击/点击”抗偶氮技术来管理CADS。我们建议将甲基丙烯酸（MAA）部分掺入牙齿材料中，并用作“可充电电池”，以结合并慢慢释放抗真菌药物。我们的初步研究表明，在固化步骤中，MAA（高达10％）可以与义齿树脂单体共聚，而不会对所得树脂的物理/机械性能产生负面影响。抗真菌药物（例如米其唑和氯己胺）可以被充电到新的义齿材料中，并慢慢释放长时间（几周或几个月）。可以通过用Quench剂（例如EDTA）处理义齿材料，可以“淬火”（被冲洗或“单击”），并可以使用相同或不同的抗真菌试剂将淬灭的义齿材料重新照射。在目前的提议中，我们将测试该技术可以使用不同的化学和生物化学结构的三种抗偶氮药物，即甲唑（米其唑），聚烯（Nystatin）和抗抗抗抗氧化抗抗菌质肽（合成）5个抗氮基（甲唑），将其应用于基于氨基甲酸酯和基于丙烯酸的义齿材料。 The specific aims of the proposed research are to: (1) fabricate new acrylic and urethane rechargeable anticandidal denture materials, and characterize the physical/mechanical properties of the new materials, (2) formulate the anticandidal drug-containing denture materials, establish drug binding/releasing kinetics, and evaluate the "click-on/click-off" anticandidal technology of the new denture materials, and (3) evaluate in体外，新义齿材料的生物相容性和抗偶性活性以及对材料的微生物耐药性的风险。新系统的生物相容性和抗偶性疗效的评估将在体外与人口腔上皮粉丝和重建的人类上皮（RHE） - 坎迪达共同培养模型一起进行。还将测试发展微生物抗性的潜在风险，以确定新方法的安全性。该项目中开发的可充电，“单击/点击”的抗偶然义齿材料可以根据存在或不存在临床念珠菌感染来激活并终止抗真菌药物治疗。可充电功能可能会允许改用更有效/有效的试剂，以增强抗偶氮效力和/或最大程度地降低真菌抗性的风险，从而导致针对CAD和其他相关疾病的个性化治疗策略。此外，这项新技术可以在其他口腔或全身性疾病和/或牙科/医疗设备的感染控制中可能用于广泛的药​​物输送系统中。