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.

该小企业技术转让 (STTR) 一期项目具有更广泛的影响/商业潜力，旨在满足对单次注射/剂量节省输送系统的强烈临床需求，该系统可以随着时间的推移以可控剂量方式在关节空间安全地释放治疗药物缓解炎症的早期治疗对于减轻与肌肉骨骼疾病相关的护理和成本负担变得越来越重要，该疾病影响着全球 17.1 亿人。包括小分子、蛋白质和生物制剂在内的多种药物将通过提供可响应不同运动类型产生的不同程度的机械力的可调药物输送系统来满足市场对改进药物输送系统的需求。与现有产品相比，该功能将减少注射次数、减少全身副作用并提高整体药物疗效，从而改善患者的生活质量和治疗结果。配送平台预计将有重大通过提高美国食品和药物管理局 (FDA) 批准的治疗方法的疗效并启用新的治疗策略，对控制肌肉骨骼疾病产生影响。这个小型企业技术转让 (STTR) 第一阶段项目旨在开发一种力刺激药物输送系统，该系统利用人体的肌肉骨骼环境的自然生理负荷，可控制几乎所有药物的释放 该技术基于专有的机械激活微胶囊的可调破裂曲线 - 减少注射次数，减少全身副作用。初步工作表明，微胶囊能够在机械力作用下封装和释放可行的生物治疗剂，提供可调节的机械激活阈值，并在活体关节内停留和破裂。该项目将进行概念验证研究，以确定机械激活微胶囊药物输送平台在生物关节环境中的可行性。这项研究将通过评估抗炎治疗来完成。白细胞介素 1 受体拮抗剂 (IL-1Ra) 的作用，该药物具有抑制急性关节炎症的能力，通过机械激活的微胶囊在已建立的白细胞介素 1-β (IL-1β) 诱导的急性关节马模型中传递与可溶性制剂相比，这项研究将为反映更具体的疾病应用、模型和最终结果的调查提供基础，从而可以评估疾病过程的长期改变。该奖项的法定使命通过使用基金会的智力优点和更广泛的影响审查标准进行评估，并被认为值得支持。