Síntese de agentes hemostáticos coagulantes e antimicrobianos baseados em materiais zeolitícos
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Data
2017-07-14
Autores
Laurenti, Juliana Bergamasco [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Apesar dos avanços na intervenção médica, hemorragia traumática fatal continua a ser uma das principais causas de morte no mundo. Nesse sentido muitos esforços têm sido dedicados à pesquisa e ao desenvolvimento de novos agentes hemostáticos que possam atuar mais efetivamente no controle de hemorragias. Embora a maior parte dos agentes hemostáticos seja de natureza orgânica, recentemente estudos envolvendo a utilização de zeólitas como agentes hemostáticos têm demonstrado resultados promissores para o controle de sangramento. Estes estudos revelam que quando em contato com o sangue, as zeólitas adsorvem rapidamente as moléculas de água, com isso, concentrando as proteínas e elementos celulares essenciais para a formação do coágulo. Além disso, a superfície da zeólita que contém cargas negativas fornece um ambiente químico favorável que funciona como um ativador de contato do padrão intrínseco do processo de coagulação. Neste contexto, os objetivos deste trabalho são as sínteses, caracterização e modulação de diferentes materiais zeolíticos nas escalas nanométricas e micrométricas (Faujasita (FAU), Gismondina (GIS), Mordenita (MOR), zeólita A (LTA), zeólita Beta (BEA), Titâno Silicato (TS-1)) juntamente com seus derivados de troca iônica para que os mesmos possam ser utilizados como agentes hemostáticos coagulantes no controle de sangramentos através da aceleração do processo de coagulação. As caracterizações fisico-química (DRX, MEV, AFM, Microscopia de contraste de fase, BET, RMN-MAS, FT-IR) mostraram que os materiais sintetizados estão de acordo com os dados reportados na literatura. Através da análise de EDS para quantificação de elementos químicos presente na estrutura zeolítica, foi possível observar que o processo de troca iônica foi satisfatório. A troca iônica com íons Ag+ mostrou-se mais eficaz, devido a substituição total dos íons Na+ pelos íons Ag+ presentes tanto nas zeólitas de escala micrométrica quanto na nanométrica. A determinação do ponto isoelétrico foi útil para prever sua natureza pro-coagulante, devido ao fato de que todos os materiais zeolíticos em ambas escalas, juntamente com os derivados de troca iônica da zeólita faujasita (troca iônica com os íons Ag+, Ba+2, Ca+2, e Mg+2) apresentaram ponto isoelétrico (p.i.) abaixo do pH sanguíneo (pH=7.0). Embora todos os materiais acima preparados tenham potencial de atuarem como agentes hemostáticos coagulantes, o estudo hemostático detalhado foi feito com as zeólitas faujasitas na escala nanométrica e micrométrica e seus derivados de troca iônica. Os melhores parâmetros tromboelastográficos (TEG) foram obtidos para a amostra Fau_Ca (zeólita faujasita micrométrica trocada com Ca2+) e NanoFau_Ca (zeólita faujasita nanométrica trocada com Ca2+). Os parâmetros R (tempo de formação do coágulo com aproximadamente 2mm), K (tempo para o coágulo atingir 20 mm) e MA (propriedade elástica da fibrina e agregação plaquetária) para o material Fau_Ca foram: R (2,3 min), K (1,2 min) e MA (55,5 mm). Os parâmetros para NanoFau_Ca foram: R (1,1 min), K (1,2 min) e MA (60,3 mm). Comparação entre os dois materiais comprovam a superioridade do material nanométrico no caso da zeólita faujasita. Dados experimentais de análises térmicas (TGA/DSC) indicaram uma diminuição da quantidade de energia liberada dos materais zeolíticos quando esses são submetidos ao processo de troca iônica. No caso da Fau_Ca e NanoFau_Ca, a análise de DSC foi de 65,8 J.g-1 e 78,21 J.g-1, respectivamente; o que é uma diminuição acentuada em relação a zeólita faujasita em suas formas sódicas: Fau (105.6 J.g-1) e a NanoFau ( 85.48 J.g-1). Análises qualitativas do efeito antimicrobiano das zeólitas NanoFau, NanoFau_Ca e NanoFau_Ag, NanoFau_Mg, NanoFau_Zn e NanoFau_Cu para os microrganismos Staphylococcus aureus ATCC 25923, Candida albicans ATCC 90028 e Candida parapsilosis ATCC 22019 foram estudadas. NanoFau_Ag foi capaz de inibir o crescimento de todos os microrganismos estudados.
Despite the advances in medical intervention, traumatic fatal hemorrhage remains a major cause of death worldwide. In this direction, many efforts have been dedicated to the research and development of new hemostatic agents that can act more effectively to control hemorrhages. Although the majority of hemostatic agents is of an organic nature recently studies involving the use of zeolites as hemostatic agents have shown encouraging results for the control of bleeding. These studies shows that when in contact with the blood, zeolites adsorbs rapidly the water molecules in their pores, thereby concentrating the proteins and cellular elements to clot formation. Moreover, the surface of the zeolite containing negative charge provides a chemical environment favorable which acts as an activator of the contact pattern of the intrinsic coagulation cascade. In this context, the main of this research are the synthesis, characterization and modulation of different zeolitic materials in both micrometric and nanometric scales (Faujasite (FAU), Gismondine (GIS), Mordenite (MOR), zeolite A (LTA), Beta zeolite (BEA), Titanium-Silicate (TS-1)) with their derivate ion exchange, so that they can be used as hemostatic agents to control bleeding by accelerating the clotting process. The physico-chemical characterizations (XRD, SEM, AFM, Phase Contrast Microscopy, BET, MAS-NRM, FTIR) showed that the synthesized materials are in agreement with data reported in the literature for these materials. Through the X-ray energy spectroscopy analysis for quantification of chemical elements present in the zeolitic structure, it was observed that the ion exchange process was effective. The ion exchange with Ag+ ions was the most efficient due to the total substitution of the Na+ ions by the Ag+ ions present for both zeolites in the micrometric and nanometric scales. The determination of the isoelectric point was useful to predict its procoagulant nature, due to the fact that zeolitic materials in both scales with ion exchange derivatives of faujasite zeolites (ion exchange with Ag+ , Ba+2, Ca+2 and Mg+2) presented isoelectric point (pi) below the blood pH (pH=7.0). Although all the above materials have the potential to act as haemostatic coagulating agents, the detailed hemostatic study was done with faujasite zeolites in the nanometric and micrometric scale and its derivatives of ionic exchange. The best thromboelastographic parameters (TEG) were obtained for the sample Fau_Ca (micrometric faujasite zeolite exchanged with Ca2+) and NanoFau_Ca (nanometric faujasite zeolite exchanged with Ca2+). The R parameters (clot formation time of approximately 2 mm), K (time for clot to reach 20 mm) and MA (elastic property of fibrin and platelet aggregation) for the material Fau_Ca were: R (2.3 min), K (1.2 min) and MA (55.5 mm). The parameters Xfor NanoFau_Ca were: R (1.1 min), K (1.2 min) and MA (60.3 mm). Comparison between the two materials confirms the superiority of the nanometric material. Experimental data from thermal analysis (TGA / DSC) indicated a decrease in the amount of energy released from the zeolitic materials when they are submitted to the ion exchange process. In the case of Fau_Ca and NanoFau_Ca the DSC analysis was 65.8 J.g -1 and 78.21 J.g -1 , respectively; which is a accentuated decrease in relation to sodium faujasite zeolite in the micrometric scale (105.6 J.g-1 ) and sodium faujasite zeolite in nanometer scale (85.48 J.g -1 ). Qualitative analysis of the antimicrobial effect of the zeolites NanoFau, NanoFau_Ca and NanoFau_Ag, NanoFau_Mg, NanoFau_Zn and NanoFau_Cu for the microorganisms Staphylococcus aureus ATCC 25923, Candida albicans ATCC 90028 and Candida parapsilosis ATCC 22019 were studied. NanoFau_Ag was able to inhibit the growth of all microorganisms studied.
Despite the advances in medical intervention, traumatic fatal hemorrhage remains a major cause of death worldwide. In this direction, many efforts have been dedicated to the research and development of new hemostatic agents that can act more effectively to control hemorrhages. Although the majority of hemostatic agents is of an organic nature recently studies involving the use of zeolites as hemostatic agents have shown encouraging results for the control of bleeding. These studies shows that when in contact with the blood, zeolites adsorbs rapidly the water molecules in their pores, thereby concentrating the proteins and cellular elements to clot formation. Moreover, the surface of the zeolite containing negative charge provides a chemical environment favorable which acts as an activator of the contact pattern of the intrinsic coagulation cascade. In this context, the main of this research are the synthesis, characterization and modulation of different zeolitic materials in both micrometric and nanometric scales (Faujasite (FAU), Gismondine (GIS), Mordenite (MOR), zeolite A (LTA), Beta zeolite (BEA), Titanium-Silicate (TS-1)) with their derivate ion exchange, so that they can be used as hemostatic agents to control bleeding by accelerating the clotting process. The physico-chemical characterizations (XRD, SEM, AFM, Phase Contrast Microscopy, BET, MAS-NRM, FTIR) showed that the synthesized materials are in agreement with data reported in the literature for these materials. Through the X-ray energy spectroscopy analysis for quantification of chemical elements present in the zeolitic structure, it was observed that the ion exchange process was effective. The ion exchange with Ag+ ions was the most efficient due to the total substitution of the Na+ ions by the Ag+ ions present for both zeolites in the micrometric and nanometric scales. The determination of the isoelectric point was useful to predict its procoagulant nature, due to the fact that zeolitic materials in both scales with ion exchange derivatives of faujasite zeolites (ion exchange with Ag+ , Ba+2, Ca+2 and Mg+2) presented isoelectric point (pi) below the blood pH (pH=7.0). Although all the above materials have the potential to act as haemostatic coagulating agents, the detailed hemostatic study was done with faujasite zeolites in the nanometric and micrometric scale and its derivatives of ionic exchange. The best thromboelastographic parameters (TEG) were obtained for the sample Fau_Ca (micrometric faujasite zeolite exchanged with Ca2+) and NanoFau_Ca (nanometric faujasite zeolite exchanged with Ca2+). The R parameters (clot formation time of approximately 2 mm), K (time for clot to reach 20 mm) and MA (elastic property of fibrin and platelet aggregation) for the material Fau_Ca were: R (2.3 min), K (1.2 min) and MA (55.5 mm). The parameters Xfor NanoFau_Ca were: R (1.1 min), K (1.2 min) and MA (60.3 mm). Comparison between the two materials confirms the superiority of the nanometric material. Experimental data from thermal analysis (TGA / DSC) indicated a decrease in the amount of energy released from the zeolitic materials when they are submitted to the ion exchange process. In the case of Fau_Ca and NanoFau_Ca the DSC analysis was 65.8 J.g -1 and 78.21 J.g -1 , respectively; which is a accentuated decrease in relation to sodium faujasite zeolite in the micrometric scale (105.6 J.g-1 ) and sodium faujasite zeolite in nanometer scale (85.48 J.g -1 ). Qualitative analysis of the antimicrobial effect of the zeolites NanoFau, NanoFau_Ca and NanoFau_Ag, NanoFau_Mg, NanoFau_Zn and NanoFau_Cu for the microorganisms Staphylococcus aureus ATCC 25923, Candida albicans ATCC 90028 and Candida parapsilosis ATCC 22019 were studied. NanoFau_Ag was able to inhibit the growth of all microorganisms studied.
Descrição
Palavras-chave
Agente hemostático, Coagulação, Hemorragia, Antimicrobiano, Zeólitas, Nanotecnologia, Hemostatic agent, Coagulation, Haemorrhage, Antimicrobial, Zeolites, Nanotechnology