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.

项目摘要 口腔溃疡是最常见的口腔疾病之一，估计患病率 美国4％。管理由未知病因疾病引起的大或多个溃疡，例如 影响全球25％的人口的侵蚀性地衣或裂开的溃疡，也是面对面的挑战 牙医和专家。口腔粘膜的溃疡会引起影响个人饮食的酸痛， 喝酒和说话；长持续的溃疡甚至会导致营养不良，从而严重影响 生活。在临床上，皮质类固醇的局部治疗仍然是口腔溃疡的一线临床疗法， 皮质类固醇是通过凝胶，口服碱（糊状）或冲洗液提供的，这些固醇提供临时 有症状的缓解。但是，当前疗法的有效性通常大大降低了 药物可以在几分钟之内通过患者的唾液稀释或消除，或通过摩擦 舌头或嘴的其他部分。此外，持续使用皮质类固醇凝胶的量 粘贴或冲洗会导致潜在的系统性影响和明显的局部副作用，例如口服念珠菌病，A 酵母菌感染进一步加剧了患者的酸痛。在此赠款申请中，我们建议 开发局部生物粘附贴片，该贴片将：1）提供单向和受控的药物释放 皮质类固醇； 2）提供障碍，以保护溃疡免受摩擦造成的疼痛； 3）避免副作用 与当前疗法相关。具体而言，我们将为粘膜开发独特的生物粘附贴 体外和体内药物输送。这种新的补丁设计既可以控制药物输送并预防药物 泄漏，从而降低局部副作用并提高治疗功效。完成 拟议的第1阶段研究将导致开发用于本地化的靶向药物输送产品 将皮质类固醇释放到粘膜表面，以在指定的时间内释放。在赠款的第2阶段中， 我们打算专注于将贴剂/药物组合疗法开发为基于临床前试验的产品 根据我们的第一阶段研究的结果。因此，我们研究的长期目标是发展生物粘附 将可广泛用于治疗多个侧面多个大型口腔溃疡的临床疗法贴入临床疗法 效果，从而减轻口腔溃疡的令人衰弱的影响，并改善生活质量 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