STTR Phase I: Mechanically Controlled Drug Delivery Platform for Joint Environments

STTR 第一阶段：用于关节环境的机械控制药物输送平台

• 批准号: 2304235
• 负责人: George Dodge
• 金额: $ 27.5万
• 依托单位: MECHANO THERAPEUTICS LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2304235&HistoricalAwards=false
• 关键词: STTR; Phase; Mechanically; Controlled; Drug

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project seeks to address the strong clinical need for a single injection/dose sparing delivery system that can safely release therapeutics in the joint space over time in a controllable dosing manner for sustained symptomatic relief. Early and efficient treatments that mitigate inflammation are becoming increasingly critical to ease the care and cost burdens associated with musculoskeletal conditions, which impact 1.71 billion people globally. The proposed platform, which can be applied to a wide variety of drugs, including small molecules, proteins, and biologics will address the market need for improved drug delivery systems by providing a tunable drug delivery system that is responsive to different degrees of mechanical force created by different movement types. The solution will allow for more precise delivery of drugs when and where they are needed. This feature will translate to fewer injections, fewer systemic side effects, and overall improved drug efficacy compared to current offerings, in turn providing improved patient quality of life and outcomes. The proposed mechano-activated drug delivery platform is expected to have a major impact in controlling musculoskeletal diseases by improving efficacy of Food and Drug Administration (FDA)-approved treatments and enabling new therapeutic strategies.This Small Business Technology Transfer (STTR) Phase I project seeks to develop a force-stimulated drug delivery system that uses the body’s natural physiological loading of musculoskeletal environments for controlled release of nearly any drug. The technology is based on the tunable rupture profile of proprietary mechano-activated microcapsules - translating to fewer injections, fewer systemic side effects, and overall improved drug efficacy. Preliminary work has demonstrated the ability of the microcapsules to encapsulate and release viable biological therapeutics upon mechanical force, to provide tunable mechano-activation thresholds, and to stay and rupture within a living joint. For this Phase I project, a proof-of-concept study will be conducted to establish the feasibility of the mechano-activated microcapsule drug delivery platform in a biological joint environment. This study will be accomplished by evaluating the anti-inflammatory therapeutic effects of interleukin-1 receptor antagonist (IL-1Ra), a drug with established ability to inhibit acute joint inflammation, delivered via mechano-activated microcapsules in an established equine model of Interleukin-1-beta (IL-1beta)-induced acute joint inflammation, in comparison to soluble formulations. This study will provide a basis for investigation into more specific disease applications, models, and terminal outcomes where modification of the disease process over the long term can be evaluated.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.

这一小型企业技术转移（STTR）I期项目的更广泛的影响/商业潜力旨在满足对单个注射/剂量保留递送系统的强烈临床需求，该临床需求可以随着时间的推移以受控剂量的方式安全地在联合空间中安全释放治疗，以持续进行症状缓解。早期有效的减轻注射的治疗方法变得越来越重要，以减轻与肌肉骨骼状况相关的伯内斯的护理和成本，这会影响全球17.1亿人。提出的平台可以应用于各种药物，包括小分子，蛋白质和生物制剂，将通过提供可调的药物输送系统来满足改善药物输送系统的市场需求，该药物递送系统对不同程度的机械力响应，由不同的运动类型产生。该解决方案将允许在需要时和何处更精确地输送药物。与当前产品相比，此功能将转化为更少的注射，更少的系统副作用以及总体上提高药物效率，从而提供改善的患者生活质量和结果。预计提议的机械激活药物输送平台有望通过改善食品和药物管理（FDA）批准的治疗方法来控制肌肉骨骼疾病，并实现新的治疗策略。 药品。该技术基于专有机械激活的微胶囊的可调破裂概况 - 转化为更少的注射，较少的全身副作用以及总体上提高的药物效率。初步工作已经证明了微胶囊在机械力上封装和释放可行的生物制剂，提供可调机制激活阈值以及在活着的关节内停留和破裂的能力。在此I阶段项目中，将进行一项概念证明研究，以确定生物学关节环境中被机理激活的微胶囊药物输送平台的可行性。这项研究将通过评估白细胞介素-1受体拮抗剂（IL-1RA）的抗炎治疗作用来完成，这是一种具有抑制急性关节感染能力的药物，该药物通过机械激活的微胶囊在固定的脑膜肠球介素1-β（IL-1BETA）固体中的促进模型中通过机械激活的微胶囊提供了脉络脉络脉络脉络脉络脉络脉络脉络脉络脉冲，从而通过机械激活的微胶囊进行了抗炎。这项研究将为对更具体的疾病应用，模型和终末结果进行投资提供基础，在这些疾病中，可以评估疾病过程的修改。该奖项反映了NSF的法定任务，并被认为是通过基金会的智力优点和更广泛的影响来通过评估来获得的支持。