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

这个小企业创新研究（SBIR）I期项目的更广泛的影响/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55万例住院治疗，死亡率高达20%。预计到2026年，胃肠道（GI）出血市场将接近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科医生或住院医生进行内窥镜检查。所提出的方法是一种可饮用的配方，用于在摄入后止血，无需内窥镜干预或住院治疗。该项目开发的技术可以应用于其他出血场景，包括野战/战斗医学或手术并发症期间出血的快速治疗。该凝胶也可用作上消化道各种疾病的药物递送载体。该小型企业创新研究（SBIR）I期项目将展示一种基于新型热敏凝胶（thermogel）配方的上消化道出血（UGIB）患者止血的新方法。该可饮用制剂在环境温度下为液体，当加热至体温时变成粘膜粘附凝胶，从而治疗上消化道出血而无需内窥镜介入。其作用基于两种协同效应：（1）粘膜粘附热凝胶的原位凝胶化提供了阻止血流的机械屏障，以及（2）出血部位的热凝胶缓慢释放药物，使愈合更快。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，并优化凝胶化温度。然后将在体外测试最佳制剂的稳定性、药物释放动力学和粘膜粘附性。最后，将在出血的临床前模型中评估所提出的方法的有效性，证明其达到止血的上级能力。该奖项反映了NSF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。

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.