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1.
Mater Sci Eng C Mater Biol Appl ; 128: 112345, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474895

RESUMO

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.


Assuntos
Ácido Hialurônico , Osteoartrite , Cartilagem , Humanos , Hidrogéis , Isotiocianatos/farmacologia , Osteoartrite/tratamento farmacológico , Poloxâmero , Sulfóxidos
2.
Mater Sci Eng C Mater Biol Appl ; 105: 110045, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546378

RESUMO

The combination of scaffolds with desirable topographic characteristics and the use of electrical stimulus consist of a strategy to repair and regenerate tissues. An interesting approach to obtain electroactive scaffolds with the aforementioned features comprises on the use of conducting polymers which can be blended with other biocompatible polymers. In this work, poly(l-lactic acid) (PLLA) and poly(ortho-ethoxyaniline) (POEA) were synthesized and PLLA/POEA mats were prepared for the first time by electrospinning technique. Topographic characterization of PLLA/POEA showed a tunable mean diameter of the nanofibers by changing the electrospinning parameters. The presence of POEA into the blend was confirmed by X-ray photoelectron and Fourier-transform infrared spectroscopy analyses. Differential scanning calorimetry curves of PLLA/POEA exhibited shift positions of Tc and absence of the exothermic peak related to the characteristic isomerization process of POEA at high temperatures. The thermal analysis results indicate a favored miscibility between the polymers which is likely resulted from the strong interaction between polymers functionalities. The homogenous distribution of POEA chains throughout the scaffold rendered redox reversibility property for the mats. Biocompatibility results showed non-cytotoxic features for PLLA/POEA, attesting this novel system as a promising candidate for biological applications.


Assuntos
Materiais Biocompatíveis/química , Teste de Materiais , Nanofibras/química , Poliésteres/química , Polietilenoglicóis/química , Linhagem Celular , Humanos
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