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

• Published in: Materials Science & Engineering C 2021-09, Vol.128, p.112345-112345, Article 112345
• Main Authors: Monteiro do Nascimento, Monica Helena, Ambrosio, Felipe Nogueira, Ferraraz, Débora Carajiliascov, Windisch-Neto, Hermann, Querobino, Samyr Machado, Nascimento-Sales, Michelle, Alberto-Silva, Carlos, Christoffolete, Marcelo Augusto, Franco, Margareth K.K.D., Kent, Ben, Yokaichiya, Fabiano, Lombello, Christiane Bertachini, de Araujo, Daniele Ribeiro
• Format: Article
• Language: English
• Subjects: Arthritis; Biocompatibility; Biomedical materials; Cartilage; Cartilage diseases; Cell lines; Chondrosarcoma; Collagen (type II); Cyclooxygenase-2; Cytokines; Cytotoxicity; Degeneration; Depletion; Drug delivery systems; Hyaluronic acid; Hybrid systems; Hydrogels; Isothiocyanate; Materials science; NF-κB protein; Osteoarthritis; Pharmacology; Poloxamer; Poloxamers; Proteoglycans; Reduction (metal working); Sulforaphane; Viscoelasticity
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2021.112345

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. [Display omitted] •Poloxamer-hyaluronic acid support osteotrophic and chondroprotective hydrogels for sulforaphane intra-articular delivery.•Hydrogels showed hyaluronic acid-dependent drug loading profiles, viscoelastic behavior, and cubic phase organization.•Hydrogels were non-cytotoxic on both osteoblast and chondrosarcoma cells.•Hydrogels inhibited proteoglycan depletion, modulated NF-κB and COX-2 and increased type II-collagen expressions.•Hydrogels were biocompatibility and efficient as delivery systems for SFN intra-articular release for OA treatment.