Enhancing the effect of fluoride for root caries control in high-risk older adults

增强氟化物对高危老年人根部龋齿控制的效果

• 批准号: 10518744
• 负责人: Livia Maria Andalo-Tenuta
• 金额: $ 37.05万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10518744
• 关键词: Acids; Address; Adult; Affect; Aging; Animals; Artificial nanoparticles; Bacteria; Binding; Buffers; Calcium Fluoride; Caries prevention; Charge; Chitosan; Clinical effectiveness; Dental Plaque; Dental caries; Dentin; Development; Diabetes Mellitus; Disease; Dose; Drops; Eating; Elderly; Electrostatics; Exhibits; Exposure to; Fluorides; Goals; Health; Hypertension; Impairment; In Vitro; Individual; Ions; Lead; Lesion; Microbial Biofilms; Minerals; Modeling; Neurodegenerative Disorders; Oral; Oral health; Outcome; Pain; Patients; Penetration; Pharmaceutical Preparations; Pilot Projects; Plant Roots; Prevalence; Preventive; Preventive treatment; Production; Quality of life; Research; Risk; Rodent; Root Caries; Safety; Saliva; Salivary; Social Functioning; Surface; Technology; Testing; Therapeutic; Therapeutic Uses; Time; Tooth Loss; Tooth root structure; Tooth structure; Toothpaste; United States; Work; Xerostomia; aging population; anticaries; bacterial metabolism; base; cariogenic bacteria; demineralization; dental biofilm; dysbiosis; frailty; high risk; human old age (65+); improved; in vivo; in vivo evaluation; innovation; mortality; nanoparticle; novel therapeutics; nutrition; oral biofilm; standard of care; systemic toxicity

PROJECT SUMMARY/ABSTRACT The problem: With an aging population, challenges to maintain good oral health are set to increase worldwide. Systemic complications (high blood pressure, diabetes, neurodegenerative disorders) add to local factors, such as the exposure of the more susceptible root surfaces and the use of medications that cause hyposalivation. Collectively, these factors increase caries rates, especially root caries, and reduce the oral health and quality of life of older adults. As oral and general health are indivisible, poor oral health outcomes in older individuals are associated with increased frailty and mortality. Challenges to overcome the increased rate of root caries in older adults include the lack of a specific approach for root caries control, the standard of care being the prescription of high fluoride toothpastes. These toothpastes have modest clinical effectiveness, since the retention of fluoride in the biofilm is not proportionally enhanced as the fluoride concentration in the product increases. Although fluoride has been the most effective agent for caries prevention for several decades, surprisingly, no innovations to improve its anticaries efficacy have been made. Hypothesis: We devised a new therapy able to enhance the anticaries effect of fluoride, while maintaining its dose and safety profile. In pilot studies, we observed that this therapy, involving the use of fluoride nanoparticles, increase by approximately 100-fold the penetration and retention of fluoride in cariogenic biofilms, and exhibit an improved fluoride- releasing profile. Thus, we hypothesize that the positively charged nanoparticles will penetrate the cariogenic biofilm, bind to negatively charged biofilm components, and release fluoride at levels high enough to improve the physicochemical effect of fluoride (needed for the control of root caries) as well as inhibit acid production by the biofilm (reducing the predominance of acid-producing species, i.e. biofilm dysbiosis). This hypothesis will be tested in the following specific aims: S.A.#1: Define the mechanisms of interaction between the therapy components and dental biofilm; S.A.#2: Determine the effects of the therapy on root dentin demineralization; S.A.#3: Establish the efficacy and safety of the therapy for caries control using in vivo rodent caries models. Significance: Upon successful completion of this project, we will understand the preventive potential of a new anticaries approach to reduce the cariogenicity of dental biofilm and control root caries. This work has the potential to exert a long-lasting impact on the control of rampant caries progression in high caries-risk groups and improve the health and quality of life of older adults suffering from hyposalivation.

项目总结/摘要 问题：随着人口老龄化，保持良好口腔健康的挑战将在全球范围内增加。 全身并发症（高血压、糖尿病、神经退行性疾病）增加了局部因素，如 因为暴露更敏感的牙根表面和使用导致唾液分泌不足的药物。 总的来说，这些因素增加了龋齿率，特别是根龋，并降低了口腔健康和质量 老年人的生活。由于口腔健康和一般健康是不可分割的，老年人的口腔健康状况不佳 与身体虚弱和死亡率增加有关。克服根面龋发病率增加的挑战 老年人包括缺乏一个具体的方法来控制根龋，护理标准是 高氟牙膏配方。这些牙膏具有适度的临床效果，因为 生物膜中氟化物的保留并不随着产品中氟化物浓度的增加而成比例地增强 增大虽然几十年来氟化物一直是预防龋齿最有效的药物， 令人惊讶的是，还没有进行改进其防龋功效的创新。假设：我们设计了一个新的 治疗能够增强氟化物的防龋效果，同时保持其剂量和安全性。在试点 研究，我们观察到，这种治疗，涉及使用氟化物纳米粒子，增加约 100-倍的渗透和保留的氟化物在致龋生物膜，并表现出改善的氟化物- 释放Profile因此，我们假设带正电荷的纳米颗粒将穿透致龋的 生物膜，与带负电荷的生物膜组分结合，并以足够高的水平释放氟化物，以改善 氟化物的物理化学作用（控制根龋所需）以及抑制酸的产生 生物膜（减少产酸物种的优势，即生物膜生态失调）。这一假设将 在以下具体目标中进行测试：S.A.# 1：定义治疗之间的相互作用机制 成分和牙齿生物膜; S.A.# 2.测定治疗对根面牙本质脱矿的影响; S.A.编号3：使用体内啮齿动物龋齿模型确定龋齿控制疗法的功效和安全性。 意义：在成功完成本项目后，我们将了解一种新的 防龋方法，以减少牙齿生物膜的致龋性和控制根龋。这项工作有 对控制高龋风险人群的猖獗龋进展产生长期影响的潜力 并改善患有唾液分泌不足的老年人的健康和生活质量。