Novel Pharmacotherapeutic Bioadhesive Patch for Oral Ulcerations

用于口腔溃疡的新型药物治疗生物粘附贴剂

• 批准号: 8714831
• 负责人: Xiaohua Liu
• 金额: $ 15.16万
• 依托单位: POST OAK PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-05 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8714831
• 关键词: 3D Print; Adrenal Cortex Hormones; Adverse effects; Affect; Aphthous Stomatitis; Applications Grants; Back; Carboxymethylcellulose; Chitosan; Clinical; Combination Drug Therapy; Computer-Aided Design; Data; Dentists; Development; Devices; Disease; Dose; Drug Controls; Drug Delivery Systems; Drug Formulations; Eating; Effectiveness; Engineering; Etiology; Extravasation; Foundations; Friction; Gel; Goals; Grant; Human; In Vitro; Individual; Infection; Lesion; Lichen Planus; Literature; Malnutrition; Mechanics; Modality; Modeling; Mouth Diseases; Oral; Oral Ulcer; Oral candidiasis; Oral cavity; Oral mucous membrane structure; Pain; Paste substance; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Polyethylene Glycols; Population; Prevalence; Property; Propionates; Quality of life; Rattus; Reporting; Research; Saliva; Side; Sodium; Specialist; Staging; Steroids; Surface; System; Techniques; Testing; Therapeutic; Time; Tongue; Treatment Efficacy; Ulcer; Work; Yeasts; base; controlled release; design; drinking; improved; in vivo; novel; phase 1 study; poly-L-lactic acid; preclinical study; prevent; product development; public health relevance

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.

项目概要 口腔溃疡是最常见的口腔疾病之一，估计患病率 美国为 4%。治疗由不明病因的疾病引起的大面积或多发性溃疡，例如 糜烂性扁平苔藓或口疮性溃疡影响着全世界 25% 的人口，这也是对 牙医和专家。口腔粘膜溃疡会引起酸痛，影响个人饮食， 喝酒、说话；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，皮质类固醇的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、口服基质（糊剂）或冲洗液输送，可提供暂时的治疗效果 症状缓解。然而，当前疗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或通过摩擦被稀释或消除。 舌头或口腔的其他部位。此外，持续使用一定量的皮质类固醇凝胶， 糊剂或冲洗剂会导致潜在的全身影响和显着的局部副作用，例如口腔念珠菌病、 酵母菌感染进一步加剧患者的疼痛。在此拨款申请中，我们建议 开发一种局部生物粘附贴片，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 与目前的治疗方法有关。具体来说，我们将开发一种独特的粘膜生物粘附贴片 体外和离体药物递送。这种新的贴片设计将控制药物输送并防止药物 渗漏，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局部靶向药物输送产品 在指定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剂/药物联合疗法开发成基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合剂 贴入临床疗法，可广泛用于治疗多发性或大面积口腔溃疡，且副作用最小 的影响，从而减轻口腔溃疡的衰弱影响，提高人们的生活质量 患者。

项目成果

Designing a Mucoadhesive ChemoPatch to Ablate Oral Dysplasia for Cancer Prevention.

• DOI: 10.1002/smll.202201561
• 发表时间: 2022-06
• 期刊: Small (Weinheim an der Bergstrasse, Germany)
• 作者: Liu X;Li Q;Wang Y;Crawford M;Bhupal PK;Gao X;Xie H;Liang D;Cheng YL;Liu X;Tsai RYL
• 通讯作者: Tsai RYL