Sulforaphane loaded hyaluronic acid poloxamer hybrid hydrogel enhances cartilage protection in osteoarthritis models

Sulforaphane SFN is an isothiocyanate with anti arthritic and immuno regulatory activities, supported by the downregulation of NF amp; 954;B pathway, reduction on metalloproteinases expression and prevention of cytokine induced cartilage degeneration implicated in OA progression. SFN promising pharmacological effects associated to its possible use, by intra articular route and directly in contact to the site of action, highlight SFN as promising candidate for the development of drug delivery systems. The association of poloxamers PL and hyaluronic acid HA supports the development of osteotrophic and chondroprotective pharmaceutical formulations. This study aims to develop PL HA hybrid hydrogels as delivery systems for SFN intra articular release and evaluate their biocompatibility and efficacy for osteoarthritis treatment. All formulations showed viscoelastic behavior and cubic phase organization. SFN incorporation and drug loading showed a concentration dependent behavior following HA addition. Drug release profiles were influenced by both diffusion and relaxation of polymeric chains mechanisms. The PL407 PL338 HA SFN hydrogel did not evoke pronounced cytotoxic effects on either osteoblast or chondrosarcoma cell lines. In vitro ex vivo pharmacological evaluation interfered with an elevated activation of NF amp; 954;B and COX 2, increased the type II collagen expression, and inhibited proteoglycan depletion. These results highlight the biocompatibility and the pharmacological efficacy of PL HA hybrid hydrogels as delivery systems for SFN intra articular release for OA treatmen