Background: Sustainedintra-articular delivery of disease modifying osteoarthritis drugs (DMOADs) holds promise for preventing the progression of PTOA. However, DMOADs are likely to work best in early disease, while patients are young and physically active. Repeated mechanical loading of joints due to strenuous activities can be detrimental for the delivery system and could affect the joint residence time and efficacy of the DMOAD.

Methods: Here, we report a hydrogel platform that can withstand repeated mechanical loading at levels comparable to the running human knee while maintaining sustained release of the encapsulated DMOAD.

Results: We found that TG-18 hydrogel has thixotropic properties: no changes were observed in the release kinetics of L-006235 or in the fibrous morphology of the hydrogel formulation after repeated cycles of mechanical loading as compared to a fresh hydrogel. Treadmill running does not affect the sustained release profile of encapsulated agents from the hydrogel in healthy mice. We show that L-006235-loaded TG-18 hydrogel (L-006235) gel prevented disease progression more effectively than free L-006235.

Conclusion: Our data provide proof of concept for DMOAD delivery via TG-18 hydrogel as a promising approach for preventing PTOA progression in physically active patients with early disease.