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ANDRADE, Laura Freitas de. Vectorization of 5-nitro-heterocyclic compounds with activity against multiresistant microorganisms. Obtaining of loaded nanoparticles and evaluation of antimicrobial activity. 2018. 110 p. Dissertation (Master's Degree in Biochemical-Pharmaceutical Technology) Faculdade de Ciências Farmacêuticas, University of São Paulo, São Paulo, 2018. Patients with burns and others extensive skin lesions show high propension to multiresistant infections. In this context, the aim of this project is to obtain chitosan nanoparticles carried with 5-nitro-heterocyclic derivate with structure analogue to nifuroxazide N'-((5-nitrofuran-2-yl) methylene)-2-benzhydrazide, that showed important activity against multiresistant bacteria strains. In its turn, the chitosan is a biopolymer with antimicrobial, analgesic, tecidual regenerator activities and by contact with excessive burns and extensive skin lesions exsudate process, form protective hydrogel films on place of application, being these activities important to infection and excessive exsudate treatment and prevention of extensive burns and lesions. The chitosan nanoparticles carried with compound (Nps-H) were obtained by ionic gelation method with sodium tripolyphosphate as crosslinker agent, varing the NaCl and polysorbate 80 concentrations in the system, oriented by factorial analyze. The Nps-H obtained were characterized by Dynamic Light Scattering (DLS) to size determination, polydispersion index (PDI) and zeta potential (ζ-P). The encapsulation efficiency (EE%) were determined by spectrophotometry UV/VIS at 370 nm by indirect method. Bepolissorbato the experiments developed, the one who showed the best results, resulted in particles with size of 321 d.nm, PDI of 0,18, ζ-P of +37 mV and EE% of 48%. The Nps-H morphology and surface were analyzed by Scanning Electronic Microscopy (SEM) and showed that Nps-H are spherical and with irregular surface. Starting of Nps-H obtain and characterization were determined the Nps-H, free compound (C-H) and empty chitosan nanoparticles (Nps-Cs) Minimal Inhibitory Concentrations (MIC) by colorimetric method and microdilution against Staphylococcus aureus ATCC 29213, ORSA and hVISA strains. The Nps-H showed the superior activity comparing to C-H and Nps-H against all strains tested. With a view to preparation of stable pharmaceutic formulation, started to Nps-H freeze-drying and with this aim, were realized Nps-H thermal analyzes by Differential Scanning Calorimetric (DSC) to determine glass transition and euthetic temperatures (Tg’ and Teut) and the cryomicroscopy analyze to determine collapse temperature (Tcol). The Nps-H samples with lyo/cryoprotectants as glycine, lactose and sucrose at different concentrations were lyophilized at -40 oC at 100 mTorr. The Nps-H samples with lactose and sucrose both at 2,5% and 5% demonstrated to preserve the original NpsH characteristics after freeze-drying process. Were observed, with the results obtained in this project that Nps-H represent the promising alternative to prevention and treatment of patients with infected skin lesions by multiresitant bacteria and to control of excessive exudate process, mainly by their therapeutic activities combined, decreasing the mortality and morbidity of these cases.

Vetorização de compostos 5-nitro-heterocí­clicos com atividade frente a microrganismos multirresistentes. &lt;i&gt;Obtenção de nanopartí­culas carregadas e avaliação da atividade antimicrobiana&lt;/i&gt;

Vetorização de compostos 5-nitro-heterocí­clicos com atividade frente a microrganismos multirresistentes. <i>Obtenção de nanopartí­culas carregadas e avaliação da atividade antimicrobiana</i>

Vetorização de compostos 5-nitro-heterocíclicos com atividade frente a microrganismos multirresistentes. <i>Obtenção de nanopartículas carregadas e avaliação da atividade antimicrobiana</i>