Synthesis of coagulant and antimicrobial hemostatic agents based on zeolite materials

Author(s)

Juliana Bergamasco Laurenti

• Document type: Doctoral Thesis
• Press: São José do Rio Preto. 2017-08-29.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto
• Defense date: 2017-07-14
• Advisor: José Geraldo Nery

Abstract

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. (AU)

• FAPESP's process: 13/16754-4 - SYNTHESIS OF COAGULANTS HEMOSTATIC AGENTS BASED IN NEW ZEOLITIC MATERIALS
• Grantee: Juliana Bergamasco Laurenti
• Support Opportunities: Scholarships in Brazil - Doctorate