I-Corps: Dentifrices With Targeted Drug Release

这个i-Corps项目的更广泛的影响/商业潜力是开发一个药物输送平台，向口腔内感兴趣的区域提供药物。目前，牙医和他们的患者的治疗选择有限。这项拟议的技术旨在将药物输送到牙齿和发炎的牙床组织，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，以减少患者对药物的暴露，并可能产生副作用，并可能将治疗选择扩大到带回家的牙膏。此外，这项拟议的技术可能会在胃部的酸性环境中提供可立即降解为无毒化合物的颗粒，从而消除了人体清除的问题，并可能允许使用比通常使用的更安全的微粒。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结果。这个i-Corps项目是基于开发一种口服药物输送平台，旨在治疗感染、疼痛和过敏等疾病。所提出的平台由羟基磷灰石、碳酸钙或柠檬酸钙的微粒组成，这些微粒负载药物(或药物鸡尾酒)，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、多西环素、洗必泰和/或强的松龙。这种微粒被设计成在特定部位的生化刺激的触发下，封闭牙本质小管和/或附着在牙床组织上，并将药物释放到口腔和牙齿的牙髓。根据化学成分的调节方式，附着力、释放率和氢气功率(PH)敏感性等因素可能会进行优化，以实现所需的性能。微粒可以作为牙膏的活性成分使用，例如牙线或牙科器械上的涂层。研究结果表明，携带丁香酚和氟化物的酪蛋白包裹的碳酸钙微球在酸性条件下被触发释放，这种条件具有致龋性细菌1或炎症组织产生的基质金属蛋白酶-7(MMP7)酶的特征。这项拟议的技术可能会更好地理解小分子、微型材料和生物组织之间相互作用的基本方面。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.