Rechargeable Long-term Anticandidal Denture Materials

可充电长期抗念珠菌义齿材料

基本信息

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
项目类别：
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

项目摘要

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）：念珠菌相关假牙口腔炎 (CADS) 是假牙佩戴者常见的、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。迄今为止，尚无有效的治疗策略来控制CADS，并且再感染率很高，特别是在老年人和身体或免疫功能低下的人中。该项目以 NIDCR（可充电长期抗真菌假牙材料，R03 DE018735）资助的试点研究为基础，将使用可充电、“点击/点击关闭”抗念珠菌技术来控制 CADS。我们已经证明，少量（10％）的甲基丙烯酸（MAA）可以在固化步骤中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。义齿树脂中的阴离子MAA部分充当“充电电池”，在很长一段时间内（数周至数月）结合并缓慢释放阳离子抗真菌药物，例如咪康唑和葡萄糖酸氯己定。通过乙二胺四乙酸 (EDTA) 处理和树脂中填充相同或不同的抗真菌药物，可以“淬灭”（洗掉）药物。在当前的项目中，我们将利用各种类别的局部抗念珠菌药物，包括唑类（克霉唑和咪康唑）、多烯（制霉菌素）和唾液抗菌多肽（合成组织素 5），将该技术应用于聚氨酯基和丙烯酸基义齿材料。。新系统的生物相容性和抗念珠菌功效将通过人口腔上皮-念珠菌和重建人上皮（RHE）-念珠菌共培养模型进行体外评估。还将测试产生微生物耐药性的风险。本研究的具体目标是：（1）制造新型丙烯酸和聚氨酯可充电抗念珠菌义齿材料，并表征新材料的物理/机械性能，（2）配制含抗念珠菌药物的义齿材料，建立药物结合/释放动力学，并评估新型义齿材料的“点击/点击”抗念珠菌技术，以及（3）体外评估新型义齿材料的生物相容性和抗念珠菌活性义齿材料和微生物对材料产生耐药性的风险。所提出的可充电、“卡扣式/卡扣式”抗念珠菌义齿材料可以根据临床需要激活或终止抗真菌药物治疗。可充电功能将允许改用更有效的药物，以增强抗念珠菌效力和/或最大限度地降低真菌耐药性的风险，从而为 CADS 和相关疾病提供个性化的治疗策略。