RESUMO
Sulforaphane (SFN) is a member of the isothiocyanate family that has anti-inflammatory action as well as anti-carcinogenic properties. The authors have devised an intra-articular injectable SFN-PLGA microsphere system that can be used for treating osteoarthritis (OA). The purpose of this study was to evaluate the in vitro and in vivo efficacy of the SFN-PLGA microsphere system. Articular chondrocytes were obtained from knee OA patients and were cultured in monolayers. The optimal concentration of SFN was obtained and the dose of SFN-PLGA microspheres was determined based on the concentration. The in vitro anti-inflammatory effect on markers such as cyclooxygenase (COX)-2, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, and matrix metalloproteinase (MMP)-2 was assessed by real-time PCR and Western blotting. The in vivo therapeutic effect of SFN-PLGA microspheres was investigated using surgically-induced rat OA model. Treatment with SFN-PLGA microspheres inhibited the mRNA and protein expression of COX-2, ADAMTS-5 and MMP-2 induced by LPS in articular chondrocytes. Intraarticular SFN-PLGA microspheres delayed the progression of surgically-induced osteoarthritis in rats. In conclusion, SFN-PLGA microspheres can be a useful injectable delivery system for treating osteoarthritis.
Assuntos
Isotiocianatos/uso terapêutico , Ácido Láctico/química , Microesferas , Osteoartrite/tratamento farmacológico , Ácido Poliglicólico/química , Idoso , Animais , Cartilagem Articular/patologia , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Citoproteção/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intra-Articulares , Isotiocianatos/administração & dosagem , Isotiocianatos/farmacologia , Masculino , Pessoa de Meia-Idade , Osteoartrite/patologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Sprague-Dawley , Sulfóxidos , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologiaRESUMO
Viable mesenchymal stem cells (MSCs) were efficiently and selectively harvested by near-infrared (NIR) light using the photothermal effect of a conductive polymer nano thin film. The poly(3,4-ethylenedioxy thiophene) (PEDOT)-coated cell culture surfaces were prepared via a simple and fast solution-casting polymerization (SCP) technique. The absorption of PEDOT thin films in the NIR region was effectively triggered cell harvesting upon exposure to an NIR source. By controlling the NIR absorption of the PEDOT film through electrochemical doping or growing PEDOT with different thin film thickness from 70 to 300 nm, the proliferation and harvesting of MSCs on the PEDOT surface were controlled quantitatively. This light-induced cell detachment method based on PEDOT films provides the temporal and spatial control of cell harvesting, as well as cell patterning. The harvested stem cells were found to be alive and well proliferated despite the use of temperature increase by NIR. More importantly, the harvested MSCs by this method preserved their intrinsic characteristics as well as multilineage differentiation capacities. This PEDOT surfaces could be used for repetitive culture and detachment of MSCs or for efficient selection or depletion of a specific subset from heterogeneous population during culture of various tissue-derived cells because there were no photodegradation and photobreakage in the PEDOT films by NIR exposure.