I-Corps: Polymer-based drug delivery system

这个I-Corps项目的更广泛的影响/商业潜力是为患有肥胖症及其相关慢性病风险（包括2型糖尿病）的患者开发安全有效的疗法。肥胖是一种复杂的疾病，其特征在于能量摄入大于消耗，导致白色脂肪组织中过量的脂质储存。拟议的创新提供了一个基于聚合物的纳米颗粒技术平台，可以有针对性地“燃烧”“坏脂肪”。成功完成拟议的活动将带来充满希望的市场机会，了解客户和战略合作伙伴的最关键需求，并确定商业化的潜力。这种控释技术平台也可以很容易地适用于治疗广泛的疾病，如脂肪肝疾病和动脉粥样硬化。这个I-Corps项目是建立在一种新型的可生物降解的聚合物为基础的纳米颗粒药物输送系统，靶向白色脂肪细胞，使持续的细胞内释放的Notch抑制剂，诱导转化为米色脂肪细胞的白色脂肪细胞，以提高能量消耗和减少肥胖。该技术将基于聚合物的药物递送的进展与对Notch信号在脂肪细胞可塑性中所起作用的理解相结合，以开发有效和安全的治疗策略来减少肥胖。肥胖是由全身能量过剩引发的，这些能量过剩以脂质的形式储存在白色脂肪细胞中，脂肪细胞的扩张导致肥胖。在白色脂肪组织中新发现的米色脂肪细胞能够积极代谢脂质以产生热量。该技术提供了优于常规药物递送的几个潜在优点，包括连续和较低剂量的药物释放、降低的成本、降低的脱靶副作用、增加的患者顺应性以及避免昂贵的外科手术。

The broader impact/commercial potential of this I-Corps project is to develop safe and effective therapies for patients suffering from obesity and its associated risks of chronic diseases, including type 2 diabetes. Obesity is a complex disorder that is characterized by greater energy intake than consumption, resulting in excessive lipid storage in the white adipose tissue. The proposed innovation offers a polymer-based nanoparticulate technology platform that enables targeted 'burning' of 'bad fat'. Successful completion of the proposed activities will enable promising market opportunities, understanding the most critical needs of customers and strategic partners, and determining the potential for commercialization. This controlled release technology platform can also be readily adapted to treat a broad spectrum of diseases such as fatty liver disease and atherosclerosis.This I-Corps project is built upon a novel biodegradable polymer-based nanoparticulate drug delivery system that targets white adipocytes and enables sustained intracellular release of Notch inhibitors to induce transformation of white adipocytes into beige adipocytes to raise energy expenditure and reduce adiposity. The technology combines advances in polymer-based drug delivery with an understanding of the role played by Notch signaling in adipocyte plasticity for the development of effective and safe therapeutic strategies to reduce adiposity. Obesity is triggered by the systemic energy surplus that is stored as lipids in white adipocytes, whose expansion leads to obesity. The newly-identified beige adipocytes in white adipose tissue are capable of actively metabolizing lipids to generate heat. This technology offers several potential advantages over conventional drug delivery including continuous and lower dosage drug release, reduced cost, decreased off-target side effects, increased patient compliance, and avoidance of expensive surgical procedures.