Rechargeable Long-term Anticandidal Denture Materials

可充电长期抗念珠菌义齿材料

• 批准号: 8579971
• 负责人: YUYU SUN
• 金额: $ 34.81万
• 依托单位: UNIVERSITY OF MASSACHUSETTS LOWELL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8579971
• 关键词: Acids; Affect; Animal Model; Antifungal Agents; Azoles; Binding; Candida; Catheters; Cessation of life; Chlorhexidine; Clinical; Clinical Trials; Coculture Techniques; Dental Care; Denture Bases; Denture Stomatitis; Denture Wear; Dentures; Device Designs; Devices; Disease; Disinfection; Drug Controls; Drug Delivery Systems; Edetic Acid; Elderly; Environment; Epithelium; Future; Glass Ionomer Cements; Grant; Habits; Health Benefit; Healthcare; Human; Immunocompromised Host; In Vitro; Individual; Infection; Kinetics; Lead; Mechanics; Mediating; Miconazole; Microbial Biofilms; Modeling; National Institute of Dental and Craniofacial Research; Natural regeneration; Nystatin; Oral health; Patients; Pharmaceutical Preparations; Pilot Projects; Plant Resins; Polyenes; Prevention; Property; Quality of life; Recurrent disease; Research; Resistance; Risk; Rotation; Salivary; Solubility; System; Systemic infection; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Tube; Urethane; Water; antimicrobial; base; biomaterial compatibility; design; effective therapy; endotracheal; fighting; gluconate; histatin 5; methacrylic acid; microbial; monomer; new technology; next generation; novel strategies; oral cavity epithelium; polypeptide; prevent; reconstitution; treatment strategy

DESCRIPTION (provided by applicant): Candida-associated denture stomatitis (CADS) is a common, recurrent disease in 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, and the reinfection rate is high, particularly in the elderly and those who are medically or immunocompromised. This project, building on our pilot studies sponsored by NIDCR (Rechargeable Long-term Antifungal Denture Materials, R03 DE018735) will use rechargeable, "click-on/click-off" anticandidal technology to control CADS. We have demonstrated that a small amount (10%) of methylacrylic acid (MAA) could be copolymerized with urethane denture resin monomers in the curing step without negatively affecting the physical/mechanical properties of the resulting resins. The anionic MAA moieties in the denture resins acted as a "rechargeable battery" to bind and then slowly release cationic antifungal drugs such as miconazole and chlorhexidine gluconate for a long period of time (weeks to months). The drugs could be "quenched" (washed out) by treating with ethylenediaminetetraacetic acid (EDTA) and the resins recharged with the same or different antifungal drugs. In the current project, we will apply this technique to both urethane-based and acrylic-based denture materials using various classes of topical anticandidal drugs, including azoles (clotrimazole and miconazole), polyene (nystatin) and salivary antimicrobial polypeptides (synthetic histatin 5). The biocompatibility and anticandidal efficacy of the new systems will be evaluated in vitro with human oral epithelium-Candida and reconstituted human epithelium (RHE)-Candida co-culture models. The risk of developing microbial resistance will also be tested. 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 proposed rechargeable, "click-on/click-off" anticandidal denture materials can activate or terminate antifungal drug treatment based on clinical needs. The rechargeable feature will allow switching to more potent/effective drugs to enhance anticandidal potency and/or minimize the risk of fungal resistance, leading to a personalized therapeutic strategy for CADS and related diseases.

描述（由申请人提供）：念珠菌相关性假牙口腔炎（CADS）是假牙佩戴者中一种常见的复发性疾病，可导致其他口腔健康问题，全身感染，生活质量下降，甚至死亡。到目前为止，还没有有效的治疗策略来控制CADS，并且再感染率很高，特别是在老年人和医学或免疫功能低下的人群中。该项目基于我们由NIDCR（可充电长期抗真菌假牙材料，R03 DE018735）资助的试点研究，将使用可充电的“点击-打开/点击-关闭”防假牙技术来控制CADS。我们已经证明，在固化步骤中，少量（10%）的甲基丙烯酸（MAA）可以与聚氨酯义齿树脂单体共聚，而不会对所得树脂的物理/机械性能产生负面影响。假牙树脂中的阴离子MAA部分充当“可充电电池”，结合并缓慢释放阳离子抗真菌药物，如咪康唑和葡萄糖酸氯己定，持续很长一段时间（数周至数月）。这些药物可以通过乙二胺四乙酸（EDTA）处理来“淬灭”（洗出），并用相同或不同的抗真菌药物重新填充树脂。在目前的项目中，我们将把这项技术应用于聚氨酯基和丙烯酸基义齿材料，使用各种类型的外用抗假牙药物，包括唑类（克霉唑和咪康唑）、多烯（制霉菌素）和唾液抗菌多肽（合成组蛋白5）。新系统的生物相容性和抗念珠菌效果将在体外用人口腔上皮-念珠菌和重组人上皮(RHE)-念珠菌共培养模型进行评估。还将测试产生微生物耐药性的风险。拟议研究的具体目的是：(1)制备新型丙烯酸和氨基甲酸乙酯可充式抗牙关义齿材料，并表征新材料的物理力学性能；(2)制备含抗牙关药物义齿材料，建立药物结合/释放动力学，评价新型义齿材料的“咔嗒/咔嗒”抗牙关技术；(3)体外评价新型义齿材料的生物相容性和抗细菌活性以及微生物对材料的耐药风险。拟议的可充电，“点击打开/点击关闭”的抗假牙材料可以根据临床需要激活或终止抗真菌药物治疗。可充电功能将允许切换到更有效的药物，以增强抗药效力和/或最大限度地降低真菌耐药的风险，从而导致针对CADS和相关疾病的个性化治疗策略。