I-Corps: Dentifrices With Targeted Drug Release

I-Corps项目更广泛的影响/商业潜力是开发一个药物输送平台，为口腔内感兴趣的区域提供药物。目前，牙医和病人的治疗选择是有限的。这项拟议的技术旨在将药物输送到牙齿和发炎的牙龈组织，以治疗感染、疼痛和过敏等疾病。这可能允许双重使用牙齿脱敏颗粒，有针对性地将药物输送到需要的区域，这可能会减少患者对药物的暴露，减少副作用，并可能扩大治疗选择，将牙科药品带回家。此外，拟议的技术可能会提供颗粒，在胃的酸性环境中立即降解为无毒化合物，这消除了从体内清除的问题，并且可能允许使用比更常用的更安全的微粒。拟议的药物输送平台可能会改善牙医的治疗选择以及患者的治疗结果。I-Corps项目的基础是开发一种口服给药平台，用于治疗感染、疼痛和过敏等疾病。所提出的平台由羟基磷灰石、碳酸钙或柠檬酸钙微粒组成，这些微粒装载有药物（或药物混合物），并用涂层或其他表面改性剂处理。典型的候选药物包括丁香酚、氟化物、强力霉素、氯己定和/或强的松龙。该微粒被设计成在被特定部位的生化刺激触发时，封闭牙本质小管和/或附着在牙龈组织上，并将货物药物释放到口腔和牙髓。根据化学调整的方式，可以优化附着力、释放速率和氢的灵敏度（pH）功率等因素，以达到所需的性能。所述微粒可作为牙膏的活性成分施用，如牙线或牙科装置上的涂层。研究结果表明，酪蛋白包被的碳酸钙微球负载丁香酚和氟化物，在酸性条件下被触发释放，这种酸性条件下存在致龋细菌1或炎症组织产生的基质金属蛋白酶-7 （MMP-7）酶。这种提出的技术可以更好地理解小分子、微尺度材料和生物组织之间相互作用的基本方面。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the development a drug delivery platform to provide medications to areas of interest within the mouth. Currently, treatment options for dentists and their patients are limited. The proposed technology is designed to deliver drugs to both teeth and inflamed gum tissue to treat conditions such as infection, pain, and hypersensitivity. This may allow dual use of tooth desensitizing particles, targeted delivery of medications to the areas in need that may reduce the patient's exposure to the medications, and side effects, and may expand treatment options to take-home dentifrices. In addition, the proposed technology may deliver particles that instantly degrade to non-toxic compounds in the acidic environment of the stomach, which eliminates the issue of clearance from the body and may allow the use of microparticles that are safer than more commonly used. The proposed drug delivery platform may improve treatment options for dentists as well as patient outcomes. This I-Corps project is based on the development of an oral drug delivery platform targeted to treat conditions such as infection, pain, and hypersensitivity. The proposed platform is composed of microparticles of hydroxyapatite, calcium carbonate, or calcium citrate that are loaded with a drug (or drug cocktail), and treated with a coating or other surface modifier. Typical drug candidates include eugenol, fluoride, doxycycline, chlorhexidine, and/or prednisolone. The microparticles are designed to occlude dentinal tubules and/or attach to the gum tissue and release the cargo drug to the oral cavity and to the pulp of the tooth when triggered by a site-specific biochemical stimulus. Depending on how the chemistry is tuned, factors such as adhesion, release rates, and power of hydrogen (pH) sensitivity may be optimized to achieve desired performance. The microparticles can be administered as an active ingredient of a dentifrice, such as a coating on dental floss or a dental device. Research results demonstrate casein-coated microspheres of calcium carbonate loaded with eugenol and fluoride are triggered to release under acidic conditions characteristic of the presence of cariogenic bacteria1 or matrix metalloproteinase-7 (MMP-7) enzyme produced by inflamed tissues. This proposed technology may provide a better understanding of the fundamental aspects of the interaction between small molecules, microscale materials, and biological tissues.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.