Novel Pharmacotherapeutic Bioadhesive Patch for Oral Ulcerations

项目摘要 口腔溃疡是最常见的口腔疾病之一，估计患病率 在美国为4%。处理由不明原因的疾病引起的大的或多个溃疡，例如 侵蚀性扁平苔藓或口腔溃疡影响全球25%的人口，也是对 牙医和专家。口腔粘膜的溃烂会导致酸痛，影响个人的饮食， 长期的溃疡甚至会导致营养不良，严重影响食物的质量。 生活。临床上，皮质类固醇局部治疗仍然是口腔溃疡的一线临床治疗方法， 皮质类固醇通过凝胶、口腔基质(糊状物)或漱口水输送，这些物质提供了暂时的 症状缓解。然而，目前的治疗方法的有效性往往因以下事实而大大降低 药物可以在几分钟内被患者的唾液稀释或消除，或者通过摩擦 舌头或嘴巴的其他部分。此外，继续使用该皮质类固醇凝胶的量， 涂抹或漱口会导致潜在的全身影响和明显的局部副作用，如口腔念珠菌病， 酵母菌感染，进一步加重患者的酸痛。在这项拨款申请中，我们建议 开发一种局部生物黏附贴片，它将：1)提供单向和受控的药物释放 皮质类固醇；2)提供屏障，保护溃疡免受摩擦引起的疼痛；3)避免副作用 与当前的治疗方法有关。具体地说，我们将为粘膜开发一种独特的生物黏附贴片 体外和体外给药。这种新的贴片设计将既控制药物输送又防止药物 渗漏，从而减少局部副作用，提高治疗效果。已完成的 拟议的第一阶段研究将导致开发针对本地化的靶向药物递送产品 在指定的时间内将皮质类固醇释放到粘膜表面。在赠款的第二阶段部分期间， 我们打算专注于将贴片/药物联合疗法开发成用于临床前试验的产品 根据我们第一阶段研究的结果。因此，我们研究的长期目标是开发一种生物粘附剂 一种可广泛用于治疗多发性或大型口腔溃疡且副作用最小的临床疗法 从而减轻口腔溃疡的虚弱作用，提高患者的生活质量 病人。

Project Summary Oral ulceration is one of the most commonly encountered oral diseases, with an estimated prevalence of 4% in the USA. Managing large or multiple ulcers that are caused by diseases of unknown etiology, such as erosive lichen planus or aphthous ulcers which affect 25% of the population worldwide, is also a challenge to dentists and specialists. Ulceration of the oral mucosa can cause soreness that affects an individual's eating, drinking, and speaking; and ulcers of long-duration can even cause malnutrition that severely affects quality of life. Clinically, topical treatment with corticosteroids remains the first-line clinical therapy for oral ulcerations, and corticosteroids are delivered through a gel, oral base (paste) or rinse which provide temporary symptomatic relief. However, the effectiveness of current therapies is often greatly reduced by the fact that the medication can be diluted or eliminated within minutes by the patient's saliva, or through rubbing against the tongue or other parts of the mouth. Furthermore, continual usage of the amounts of the corticosteroid gel, paste, or rinse leads to potential systemic effects and significant local side effects, such as oral candidiasis, a yeast infection which further exacerbates the patient's soreness. In this grant application, we propose to develop a topical bioadhesive patch that will: 1) provide unidirectional and controlled drug release of corticosteroids; 2) provide a barrier to protect the ulcers from pain caused by friction; and 3) avoid side effects associated with current therapies. Specifically, we will develop a unique bioadhesive patch for the mucosal drug delivery in vitro and ex vivo. This new patch design will both control drug delivery and prevent drug leakage, thereby decreasing local side effects and increasing the therapeutic efficacy. Completion of the proposed Phase 1 research will result in the development of a targeted drug delivery product for localized release of corticosteroids to the mucosal surface for designated time. During the Phase 2 portion of the grant, we intend to focus on developing the patch/drug combination therapy into a product for preclinical trials based upon the results of our Phase 1 study. Thus the long-term goal of our research is to develop a bioadhesive patch into a clinical therapy that can be widely used to treat multiple or large oral ulcers with minimal side effects, thereby alleviating the debilitating effects of oral ulcerations and improving the quality of life for the patients.