Sulforaphane-loaded hyaluronic acid-poloxamer hybrid hydrogel enhances cartilage protection in osteoarthritis models.
Autor: | Monteiro do Nascimento MH; Human and Natural Sciences Center, ABC Federal University, Santo André, SP, Brazil; Drugs and Bioactives Delivery Systems Research Group - SISLIBIO, Federal University of ABC. Santo André, SP, Brazil., Ambrosio FN; Engineering, Modelling and Applied Social Sciences Center, ABC Federal University, Santo André, SP, Brazil., Ferraraz DC; Engineering, Modelling and Applied Social Sciences Center, ABC Federal University, Santo André, SP, Brazil., Windisch-Neto H; Engineering, Modelling and Applied Social Sciences Center, ABC Federal University, Santo André, SP, Brazil., Querobino SM; Human and Natural Sciences Center, ABC Federal University, Santo André, SP, Brazil., Nascimento-Sales M; Human and Natural Sciences Center, ABC Federal University, Santo André, SP, Brazil., Alberto-Silva C; Human and Natural Sciences Center, ABC Federal University, Santo André, SP, Brazil., Christoffolete MA; Human and Natural Sciences Center, ABC Federal University, Santo André, SP, Brazil., Franco MKKD; Instituto de Pesquisas Energéticas e Nucleares-IPEN, São Paulo, SP, Brazil., Kent B; Institute for Soft Matter and Functional Materials, Helmholtz-Zentrum Berlin für Materialien, Berlin, Germany; School of Chemistry, University of New South Wales, Kensington, Australia., Yokaichiya F; Department Quantum Phenomena in Novel Materials Helmholtz-Zentrum Berlin für Materialien, Berlin, Germany; Department of Physics, Federal University of Parana, Curitiba, Paraná, Brazil., Lombello CB; Engineering, Modelling and Applied Social Sciences Center, ABC Federal University, Santo André, SP, Brazil., de Araujo DR; Human and Natural Sciences Center, ABC Federal University, Santo André, SP, Brazil; Drugs and Bioactives Delivery Systems Research Group - SISLIBIO, Federal University of ABC. Santo André, SP, Brazil. Electronic address: daniele.araujo@ufabc.edu.br. |
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Jazyk: | angličtina |
Zdroj: | Materials science & engineering. C, Materials for biological applications [Mater Sci Eng C Mater Biol Appl] 2021 Sep; Vol. 128, pp. 112345. Date of Electronic Publication: 2021 Jul 31. |
DOI: | 10.1016/j.msec.2021.112345 |
Abstrakt: | 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.) |
Databáze: | MEDLINE |
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