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

该小型企业技术转让（STTR）I期项目的更广泛影响/商业潜力旨在满足对单次注射/剂量节省给药系统的强烈临床需求，该系统可以随着时间的推移以可控给药方式在关节间隙中安全释放治疗药物，以持续缓解症状。缓解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成本负担变得越来越重要，这些疾病影响着全球17.1亿人。所提出的平台可应用于各种药物，包括小分子、蛋白质和生物制剂，将通过提供响应于由不同运动类型产生的不同程度的机械力的可调药物递送系统来满足市场对改进的药物递送系统的需求。 该解决方案将允许在需要的时间和地点更精确地输送药物。与目前的产品相比，这一功能将转化为更少的注射，更少的全身副作用和整体改善的药物疗效，从而提高患者的生活质量和结果。该机械激活药物输送平台有望通过提高美国食品药品监督管理局（FDA）批准的治疗方法的疗效和实现新的治疗策略，对控制肌肉骨骼疾病产生重大影响。该小企业技术转让（STTR）第一阶段项目旨在开发一种力量-受刺激的药物输送系统，利用人体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。该技术基于专有的机械激活微胶囊的可调破裂轮廓-转化为更少的注射，更少的全身副作用和整体改善的药物疗效。初步工作已经证明了微胶囊在机械力下封装和释放可行的生物治疗剂的能力，以提供可调的机械激活阈值，并在活关节内停留和破裂。对于这个I期项目，将进行概念验证研究，以确定机械活化微胶囊药物递送平台在生物联合环境中的可行性。本研究将通过评估白细胞介素-1受体拮抗剂（IL-1 Ra）的抗炎治疗作用来完成，白细胞介素-1受体拮抗剂（IL-1 Ra）是一种具有抑制急性关节炎症能力的药物，通过机械活化微胶囊在已建立的白细胞介素-1-β（IL-1 β）马模型中递送。诱导的急性关节炎症，与可溶性制剂进行比较。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，其中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 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.