SBIR Phase I: A thermogel-based drug delivery platform for the upper gastrointestinal bleeding treatment

SBIR 第一期：基于热凝胶的药物递送平台，用于治疗上消化道出血

• 批准号: 2014730
• 负责人: JEFFREY LINHARDT
• 金额: $ 22.5万
• 依托单位: INTACT THERAPEUTICS
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2022-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2014730&HistoricalAwards=false
• 关键词: SBIR; Phase; thermogel; based; drug

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to develop an innovative method to treat upper gastrointestinal bleeding (UGIB). UGIB results in more than 550,000 hospitalizations per year in the US alone with a mortality rate of up to 20%. The gastrointestinal (GI) bleeding market is projected to be nearly USD 1 billion by 2026, with the overall hemostatic agents market reaching over USD 5 billion. Current solutions require endoscopy performed by a specialist or hospital admission. The proposed approach is a drinkable formulation to stop bleeding after ingestion, eliminating the need for endoscopic intervention or hospitalization. The technology developed in this project could then be applied to other bleeding scenarios, including field/combat medicine or rapid treatment of hemorrhage during surgical complications. The gel can also be used as a drug delivery vehicle for a variety of disorders of the upper GI tract.This Small Business Innovation Research (SBIR) Phase I project will demonstrate a new approach to achieve hemostasis in patients with upper gastrointestinal bleeding (UGIB), based on a novel thermosensitive gel (thermogel) formulation. The drinkable formulation is liquid at ambient temperature and becomes a mucoadhesive gel when warmed to body temperature, thereby treating hemorrhage in the upper GI tract without the need for endoscopic intervention. Its action is based on two synergistic effects: (1) The in situ gelation of the mucoadhesive thermogel provides a mechanical barrier against blood flow, and (2) the slow release of drugs from the thermogel at the hemorrhage site enables more rapid healing. Initial efforts will be dedicated to formulation development wherein compatibility of the thermogel with different drug candidates will be evaluated, and optimization of the gelation temperature will be performed. The best formulations will then be tested in vitro for stability, drug release kinetics, and mucoadhesion. Finally, the effectiveness of the proposed approach will be assessed in preclinical models of bleeding, demonstrating its superior ability to reach hemostasis. This is expected to apply to disorders including gastroesophageal reflux disease, eosinophilic esophagitis, and oral mucositis.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.

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力是开发一种治疗上消化道出血（UGIB）的创新方法。仅在美国，UGIB每年就导致超过55万人住院，死亡率高达20%。到2026年，胃肠道出血市场预计将接近10亿美元，整体止血剂市场将超过50亿美元。目前的解决方案需要由专家或住院进行内窥镜检查。建议的方法是一种可饮用的配方，在摄入后止血，消除了内镜干预或住院的需要。在这个项目中开发的技术可以应用于其他出血情况，包括战场/战斗医学或手术并发症期间出血的快速治疗。该凝胶也可作为多种上消化道疾病的药物递送载体。这项小型企业创新研究（SBIR）一期项目将展示一种基于新型热敏凝胶（thermogel）配方的新方法，以实现上消化道出血（UGIB）患者的止血。该可饮用配方在室温下为液体，加热至体温时变为黏附凝胶，无需内镜干预即可治疗上消化道出血。它的作用基于两种协同作用：(1)黏附热凝胶的原位凝胶为血液流动提供了机械屏障；(2)从出血部位的热凝胶中缓慢释放药物，可以更快地愈合。最初的努力将致力于配方开发，其中将评估热凝胶与不同候选药物的相容性，并将进行凝胶温度的优化。然后将对最佳配方进行体外稳定性、药物释放动力学和黏附性测试。最后，该方法的有效性将在临床前出血模型中进行评估，以证明其达到止血的卓越能力。这有望应用于胃食管反流病、嗜酸性粒细胞性食管炎和口腔黏膜炎等疾病。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。