RESUMO
Anti-tumor necrosis factor α (TNFα) drugs such as etanercept (ETN) have been mostly used in systemic treatment of rheumatoid arthritis. To eliminate the side effects in long-term treatments and to achieve a local sustained anti-inflammatory effect, a controlled drug delivery system is needed for anti-TNFα drugs. This study aims to develop novel injectable microcarriers of ETN that can provide long-term controlled release of this protein drug upon intra-articular application. In this study, poly(ε-caprolactone) (PCL) and its copolymer with poly(ethylene glycol), methoxypoly(ethylene glycol)-poly(ε-caprolactone)-methoxypoly(ethylene glycol) microspheres (MPEG-PCL-MPEG) were compared for their prospective success in rheumatoid arthritis treatment. Microspheres with smooth surface of a mean particle diameter of approximately 5 µm were prepared with both polymers. MPEG-PCL-MPEG microspheres had higher encapsulation efficiency than PCL microspheres. The activity of encapsulated ETN within MPEG-PCL-MPEG microspheres also retained while 90% of the activity of ETN within PCL microspheres could retain during 90-day release. MPEG-PCL-MPEG microspheres showed faster ETN release compared to PCL microspheres in various release media. Cumulative amounts of ETN released from both types of microspheres were significantly lower in cell culture medium and in synovial fluids than in phosphate buffered saline. This was mainly due to protein adsorption onto microspheres. Hydrophilic MPEG segment enhanced ETN release while preventing protein adsorption on microspheres compared to PCL. Sustained ETN release from microspheres resulted with a significant decrease in pro-inflammatory cytokines (TNFα, IFNγ, IL-6, IL-17) and MMP levels (MMP-3, MMP-13), while conserving viability of fibroblast-like synoviocytes compared to the free drug. Results suggest that MPEG-PCL-MPEG is a potential copolymer of PCL that can be used in development of biomedical materials for effective local treatment purposes in chronic inflammatory arthritis owing to enhanced hydrophilicity. Yet, PCL microspheres are also promising systems having good compatibility to synoviocytes and would be especially the choice for treatment approach requiring longer term and slower release.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos , Imunoglobulina G/administração & dosagem , Receptores do Fator de Necrose Tumoral/administração & dosagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Preparações de Ação Retardada , Etanercepte , Humanos , Técnicas In Vitro , Mediadores da Inflamação/metabolismo , Injeções Intra-Articulares , Teste de Materiais , Metaloproteinases da Matriz/metabolismo , Microesferas , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patologiaRESUMO
Polyester-polyether type block copolymers have attracted attention in the area of drug delivery systems with their capability in providing a broad range of amphiphilic characteristics. The aim of the present work was to prepare and characterize immunoglobulin G (IgG) loaded methoxy poly(ethylene glycol)-poly(É-caprolactone)-methoxy poly(ethylene glycol) (MPEG-PCL-MPEG) microspheres as potential carrier for therapeutic monoclonal antibodies used in clinics. MPEG-PCL-MPEG triblock copolymer was synthesized by ring-opening polymerization of É-caprolactone initiated by MPEG and then characterized. Microspheres were prepared by double emulsion-solvent evaporation method and their properties were compared with those of PCL microspheres. Microspheres had spherical shape with a mean particle size around 6 µm. MPEG-PCL-MPEG microspheres had higher encapsulation efficiency than PCL microspheres. After 90 days of release, 30±2% and 57±3% of the bioactivity of IgG released from non-irradiated PCL and MPEG-PCL-MPEG microspheres were protected, respectively. Presence of MPEG in microspheres provided more controlled IgG release rate and protected IgG from denaturation during γ-irradiation (20±3% and 49±2% for PCL and MPEG-PCL-MPEG microspheres, respectively). In vitro cytotoxicity tests revealed that both MPEG-PCL-MPEG and PCL microspheres had no toxic effect on cells. This study showed that MPEG-PCL-MPEG microspheres are promising delivery systems for therapeutic monoclonal antibodies.
Assuntos
Imunoglobulina G/metabolismo , Microesferas , Poliésteres/química , Polietilenoglicóis/química , Células 3T3 , Animais , Raios gama , Humanos , Cinética , Camundongos , Microscopia Eletrônica de Varredura , Peso Molecular , Tamanho da Partícula , Poliésteres/síntese química , Polietilenoglicóis/síntese química , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The aim of this study was to determine the effect of autoclave polymerization on the transverse strength of denture base polymers. To this end, 30 rectangular test specimens were fabricated of two heat-polymerized denture base polymers. The test groups were: (I) control, i.e., conventional water bath to polymerize resins by heat at 100 degrees C for 30 minutes; (II) autoclave polymerization at 60 degrees C for 30 minutes followed by 130 degrees C for 10 minutes; and (III) autoclave polymerization at 60 degrees C for 30 minutes followed by 130 degrees C for 20 minutes. The specimens were tested with three-point bending test at a crosshead speed of 5 mm/min. It was revealed that the transverse strength of specimens increased with statistical significance when the autoclave was used for polymerization.
Assuntos
Resinas Acrílicas/química , Bases de Dentadura , Polimetil Metacrilato/química , Análise do Estresse Dentário , Dureza , Temperatura Alta , Teste de Materiais , Fatores de TempoRESUMO
With a view to understanding the structure-property relation of a silicone-based soft lining denture material after polymerization, its chemical composition and viscoelastic properties were investigated. Chemical compositions of the cured and uncured polymers of a commercial silicone permanent soft liner were determined by infrared spectroscopic analysis, nuclear magnetic resonance (NMR), and X-ray photoelectron spectroscopy. Dynamic mechanical analysis (DMA) method was used to investigate the viscoelastic behavior of the cured polymer of liner. Spectroscopic analysis showed that the main component of soft liner was vinyl-terminated poly(dimethylsiloxane), and the adhesive was 3-methacryloxypropyltrimethoxy silane. NMR results revealed that other components included benzoyl peroxide as initiator for polymerization and also silicilic acid. Surface analysis by XPS provided interesting insights about the nature of adhesive bonding, as well as diffusion of silicilic acid through the matrix of the processed material and leaching-out. DMA results showed a two-phase character, and that the cured polymer was highly elastic.
Assuntos
Reembasadores de Dentadura , Polimetil Metacrilato/química , Bases de Dentadura , Dimetilpolisiloxanos/química , Espectroscopia de Ressonância Magnética/métodos , Nylons/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Propriedades de SuperfícieRESUMO
In this study, several provisional resin materials were investigated by dynamic mechanical analysis (DMA). The materials were autopolymerized PMMA and PEMA, light cured PMMA. Autopolymerized PMMA has the highest T(g) (131 degrees C) compared to that of the autopolymerized PEMA (102 degrees C) and light cured PMMA (120 degrees C). The storage moduli for autopolymerized PMMA, autopolymerized PEMA and light cured PMMA are 2.9, 1.8 and 2.3 GPa, respectively. The loss moduli of the same resins are 330, 300 and 350 MPa, respectively. Each of these resins were reinforced with 1%, 3% and 5% of each of metal oxides of MgO, ZrO2 and Al2O3 and then studied with DMA. Small changes were observed for dynamic mechanical properties tested. However, the changes are not systematic and noticeable. This is most probably due to smaller size of metal oxides particles compared to that of polymer particle size.