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

Autor(es):Mostrar menos -

Monteiro do Nascimento, Monica Helena ^{[1, 2]} ; Ambrosio, Felipe Nogueira ^[3] ; Ferraraz, Debora Carajiliascov ^[3] ; Windisch-Neto, Hermann ^[3] ; Querobino, Samyr Machado ^[1] ; Nascimento-Sales, Michelle ^[1] ; Alberto-Silva, Carlos ^[1] ; Christoffolete, Marcelo Augusto ^[1] ; Franco, Margareth K. K. D. ^[4] ; Kent, Ben ^{[5, 6]} ; Yokaichiya, Fabiano ^{[7, 8]} ; Lombello, Christiane Bertachini ^[3] ; de Araujo, Daniele Ribeiro ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] ABC Fed Univ, Human & Nat Sci Ctr, Santo Andre, SP - Brazil

^[2] Fed Univ ABC, Drugs & Bioact Delivery Syst Res Grp SISLIBIO, Santo Andre, SP - Brazil

^[3] ABC Fed Univ, Engn Modelling & Appl Social Sci Ctr, Santo Andre, SP - Brazil

^[4] Inst Pesquisas Energet & Nucl IPEN, Sao Paulo, SP - Brazil

^[5] Helmholtz Zentrum Berlin Mat, Inst Soft Matter & Funct Mat, Berlin - Germany

^[6] Univ New South Wales, Sch Chem, Kensington, NSW - Australia

^[7] Univ Fed Parana, Dept Phys, Curitiba, Parana - Brazil

^[8] Helmholtz Zentrum Berlin Mat, Dept Quantum Phenomena Novel Mat, Berlin - Germany

• Tipo de documento: Artigo Científico
• Fonte: Materials Science & Engineering C-Materials for Biological Applications; v. 128, SEP 2021.
• Citações Web of Science: 0

Resumo

Sulforaphane (SFN) is an isothiocyanate with anti-arthritic and immuno-regulatory activities, supported by the downregulation of NF-kappa B pathway, reduction on metalloproteinases expression and prevention of cytokineinduced 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 concentrationdependent 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-kappa 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 treatment. (AU)

• Processo FAPESP: 19/20303-4 - Organogéis termosensíveis como estratégias para o tratamento de processos inflamatórios: da estrutura supramolecular à avaliação farmacológica
• Beneficiário: Daniele Ribeiro de Araujo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/14457-5 - Carreadores baseados em lipídios (SLN/NLC e lipossomas com gradiente iônico) como estratégia para aumentar a encapsulação e a potência de anestésicos locais
• Beneficiário: Eneida de Paula
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/14763-1 - Hidrogéis de poloxamer-ácido hialurônico como sistemas para liberação de sulforafano no tratamento da osteoartrite
• Beneficiário: Mônica Helena Monteiro Do Nascimento
• Modalidade de apoio: Bolsas no Brasil - Doutorado