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

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._x000D_ _x000D_ 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._x000D_ _x000D_ 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.