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.

项目摘要/摘要 问题：随着人口老龄化，维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，例如 作为更易感的根部表面的暴露以及导致缺乏症的药物的使用。 总的来说，这些因素增加了龋齿率，尤其是根龋，并降低了口腔健康和质量 老年人的生活。由于口腔和一般健康是不可分割的，老年人的口腔健康状况不佳 与脆弱和死亡率的增加有关。克服根源龋齿率提高的挑战 老年人包括缺乏根系控制的特定方法，护理标准是 高氟化物牙膏的处方。这些牙膏具有适中的临床有效性，因为 随着产品中的氟化物浓度，氟化物在生物膜中的保留不会成比例地增强 增加。尽管氟化物一直是预防龋齿的最有效药物，但 令人惊讶的是，尚未提高其抗体功效的创新。假设：我们设计了一个新的 能够增强氟化物的耐药作用，同时保持其剂量和安全性。在飞行员中 研究，我们观察到，这种涉及使用氟纳米颗粒的疗法大约增加 100倍氟化物在富富生物膜中的渗透和保留，并具有改善的氟化物 - 释放配置文件。因此，我们假设带正电荷的纳米颗粒将穿透致癌 生物膜，与带负电荷的生物膜组件结合，并在足够高的水平上释放氟化物 氟化物的物理化学作用（控制根龋齿需要），并抑制酸的产生 生物膜（降低产生酸性物种的占主导地位，即生物膜营养不良）。这个假设将会 在以下特定目的中进行测试：S.A.＃1：定义治疗之间的相互作用机制 成分和牙科生物膜； S.A.＃2：确定治疗对根牙本质脱矿的影响； S.A.＃3：使用体内啮齿动物龋齿模型来确定治疗疗法的疗效和安全性。 意义：成功完成该项目后，我们将了解新的预防潜力 抗药方法可降低牙齿生物膜和控制根龋的致富性。这项工作有 可能对高性风风险基团猖caries进展的控制产生持久影响 并改善患有损失的老年人的健康和生活质量。