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

Materials science & engineering. C, Materials for biological applications 2021 Sep

filter terms:

Sulforaphane (SFN) is an isothiocyanate with anti-arthritic and immuno-regulatory activities, supported by the downregulation of NF-κB 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-κB 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 treatment. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Monica Helena Monteiro do Nascimento, Felipe Nogueira Ambrosio, Débora Carajiliascov Ferraraz, Hermann Windisch-Neto, Samyr Machado Querobino, Michelle Nascimento-Sales, Carlos Alberto-Silva, Marcelo Augusto Christoffolete, Margareth K K D Franco, Ben Kent, Fabiano Yokaichiya, Christiane Bertachini Lombello, Daniele Ribeiro de Araujo. Sulforaphane-loaded hyaluronic acid-poloxamer hybrid hydrogel enhances cartilage protection in osteoarthritis models. Materials science & engineering. C, Materials for biological applications. 2021 Sep;128:112345