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，据估计患病率 4%在美国。管理由病因不明的疾病引起的大溃疡或多发性溃疡，例如 侵蚀性扁平苔藓或阿弗他溃疡影响全世界25%的人口， 牙医和专家。口腔粘膜溃疡可引起疼痛，影响个体进食， 长期的溃疡甚至会导致营养不良，严重影响饮食质量。 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， 和皮质类固醇通过凝胶、口腔基质（糊剂）或冲洗剂递送， 症状缓解。然而，当前疗法的有效性通常由于以下事实而大大降低： 药物可以在几分钟内被病人的唾液稀释或消除，或者通过摩擦皮肤， 舌头或口腔的其他部位。此外，连续使用皮质类固醇凝胶的量， 糊剂或冲洗剂导致潜在的全身效应和显著的局部副作用，例如口腔念珠菌病， 酵母菌感染进一步加剧了患者的疼痛。在这项拨款申请中，我们建议 开发局部生物粘附贴剂，其将：1）提供单向和受控的药物释放， 皮质类固醇; 2）提供屏障以保护溃疡免受摩擦引起的疼痛;以及3）避免副作用 与目前的治疗有关。具体来说，我们将开发一种独特的生物粘附贴片， 体外和离体药物递送。这种新的贴片设计将既控制药物输送，又防止药物 从而减少局部副作用并提高治疗效果。完成 拟议的第一阶段研究将导致开发一种靶向药物输送产品，用于局部化 皮质类固醇释放到粘膜表面指定的时间。在赠款的第二阶段， 我们打算专注于将贴剂/药物联合疗法开发成一种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 可广泛用于治疗多发性或大面积口腔溃疡， 效果，从而减轻口腔溃疡的衰弱作用，并改善患者的生活质量。 患者

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.