RESUMO
The aim of this work was to evaluate the effects of incorporating thrombin in arabinogalactan (AG)/ß-glucan (BG)-based carriers. The products were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray powder diffraction (XRPD) and X-ray photoelectron spectroscopy techniques. Results, especially deconvoluted XRPD patterns indicated creation of new phases and potential complex formation. Results also highlighted that the AG carrier leads to higher residual thrombin-specific activity, while the in vivo haemostatic effect was enhanced when insoluble BG was present in the matrix. Our results confirm that thrombin can be successfully added to the carriers and that these materials are promising alternatives to standard vehicles.
Assuntos
Portadores de Fármacos , Galactanos , Trombina/administração & dosagem , beta-Glucanas , Animais , Portadores de Fármacos/química , Feminino , Galactanos/química , Hemostasia/efeitos dos fármacos , Humanos , Masculino , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Espectroscopia Fotoeletrônica , Difração de Pó , Ratos Wistar , Proteínas Recombinantes/administração & dosagem , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , beta-Glucanas/químicaRESUMO
Recombinant human thrombin (rhThrombin) is a potential hemostatic alternative to bovine and human plasma-derived thrombin. Hemostatic, liver regeneration effect and plasma concentrations of rhThrombin (SCILL) tested in the form of solution and hydrogels (thermo-sensitive poloxamer gel and carbomer gel; hameln rds) were evaluated. In the bleeding model, rhThrombin was applied locally on the bleeding site. The time to hemostasis was measured. The rhThrombin in liquid form as well as the thermo-sensitive gel forming formulation significantly reduced the bleeding time in comparison to saline. In the regeneration model, a cut in the form "V" was made on the liver and rhThrombin in both formulations was applied at defined concentrations to the wound for 5 min. The rats survived 1, 3 and 5 days after the injury and treatment. Histological examination showed better results in the group treated with rh Thrombin gel in comparison to the liquid form - solution; differences were insignificant. Low [(125)I]-rhThrombin radioactivity was evaluated in plasma after topical application (solution and both hydrogels) at hemostatic effective doses to partial hepatectomy in rats. Locally applied rh Thrombin on the rat damaged liver tissue never reached pharmacologically active systemic levels. The plasmatic levels and the content of this active protein in injured liver tissue were lower after application of its hydrogels versus solution.
