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

这一小型企业技术转让(STTR)第一阶段项目的更广泛的影响/商业潜力旨在满足对单一注射/节省剂量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的剂量方式在关节间隙安全地释放治疗药物，以持续缓解症状。减轻炎症的早期有效治疗对于减轻与肌肉骨骼疾病相关的护理和费用负担正变得越来越关键，这些疾病影响着全球17.1亿人。拟议的平台可应用于各种药物，包括小分子、蛋白质和生物制品，它将通过提供一种可调节的药物输送系统来满足市场对改进药物输送系统的需求，该系统可响应不同运动类型产生的不同程度的机械力。该解决方案将允许在需要的时间和地点更精确地运送药物。与目前的产品相比，这一功能将转化为更少的注射，更少的全身副作用，以及总体上更好的药物疗效，进而提高患者的生活质量和结果。拟议的机械激活药物传递平台有望通过提高食品和药物管理局(FDA)批准的治疗方法的疗效和实现新的治疗策略，在控制肌肉骨骼疾病方面产生重大影响。这个小企业技术转移(STTR)第一阶段项目旨在开发一种力刺激药物传递系统，该系统利用人体对肌肉骨骼环境的自然生理负荷来控制几乎任何药物的释放。这项技术是基于专有的机械激活微囊的可调破裂曲线-转化为更少的注射，更少的全身副作用，以及整体改善的药物疗效。初步工作表明，微囊能够在机械力的作用下包裹和释放可行的生物疗法，提供可调的机械激活阈值，并在活体关节内停留和破裂。对于这个第一阶段的项目，将进行概念验证研究，以确定在生物联合环境中机械激活微胶囊给药平台的可行性。这项研究将通过评估IL-1受体拮抗剂(IL-1ra)的抗炎治疗效果来完成，IL-1ra是一种公认的抑制急性关节炎症的药物，通过机械激活微囊在已建立的白细胞介素1-β(IL-1β)诱导的急性关节炎症的马模型中给药，与可溶性制剂相比较。这项研究将为更具体的疾病应用、模型和最终结果的调查提供基础，在那里可以评估疾病过程的长期修改。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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 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.