The local delivery of drugs to joints is a recognized strategy in the treatment of osteoarthritis. Hydrogels, particularly those that can be injected as liquids but undergo gelation in the joint, are promising platforms for intra-articular drug delivery. However, their properties must be carefully designed and tuned to achieve sustained drug release, which has been a challenge with previous hydrogels. We describe here the use of a combination of non-covalent thermal gelation and covalent cross-linking with poly(caprolactone-co-lactide)(PCLA)-poly(ethylene glycol)(PEG)-PCLA triblock copolymers to achieve hydrogels with sustained drug release in joints. The hybrid cross-linking approach afforded higher viscoelastic and compression moduli compared to non-covalent cross-linking alone and enabled celecoxib as well as other drugs to be loaded without substantially compromising the mechanical properties. Celecoxib release in vitro was much slower for the hybrid cross-linked hydrogel, with only 20% released over 22 days, compared to 90% released over 22 days for a non-covalently cross-linked hydrogel. Furthermore, the burst release of celecoxib was reduced in vivo in horse joints compared to non-covalent systems, and drug was detected in synovial fluid for a period of two months. Overall, this new hydrogel system shows significant promise as a platform for further development in intra-articular delivery.
Available at: http://works.bepress.com/frank-beier/66/