A Nanostructured Lipid System to Improve the Oral Bioavailability of Ruthenium(II) Complexes for the Treatment of Infections Caused by Mycobacterium tuberculosis

Tuberculosis (TB) is an infectious, airborne disease caused by the bacterium Mycobacterium tuberculosis that mainly affects the lungs. Fortunately, tuberculosis is a curable disease, and in recent years, death rates for this disease have decreased. However, the existence of antibiotic-resistant strains and the occurrence of co-infections with human immunodeficiency virus (HIV), have led to increased mortality in recent years. Another area of concern is that one-third of the world′s population is currently infected with M. tuberculosis in its latent state, serving as a potential reservoir for active TB. In an effort to address the failure of current TB drugs, greater attention is being given to the importance of bioinorganic chemistry as an ally in new research into the development of anti-TB drugs. Ruthenium (Ru) is a chemical element that can mimic iron (Fe) in the body. In previous studies involving the following heteroleptic Ru complexes, [Ru(pic)(dppb)(bipy)]PF6 (SCAR1), [Ru(pic)(dppb)(Me-bipy)]PF6 (SCAR2), [Ru(pic)(dppb)(phen)]PF6 (SCAR4), cis-[Ru(pic)(dppe)2]PF6 (SCAR5), and [Ru(pic)(dppe)(phen)]PF6 (SCAR7), we observed excellent anti-TB activity, moderate cell-toxicity, and a lack of oral bioavailability in an in vivo model of these complexes. Therefore, the objective of this study was to evaluate the toxicity and oral bioavailability of these complexes by loading them into a nanostructured lipid system. The nanostructured lipid system was generated using different ratios of surfactant (soybean phosphatidylcholine, Eumulgin®, and sodium oleate), aqueous phase (phosphate buffer with a concentration of 1X and pH 7.4), and oil (cholesterol) to generate a system for the incorporation of Ru(II) compounds. The anti-TB activity of the compounds was determined using a microdilution assay with Resazurin (REMA) against strains of M. tuberculosis H37Rv and clinical isolates resistant. Cytotoxicity assay using J774.A1 cells (ATCC TIB-67) and intra-macrophage activity were performed. The oral bioavailability assay was used to analyze blood collected from female BALB/C mice. Plasma collected from the same mice was analyzed via inductively coupled plasma mass spectrometry (ICP-MS) to quantify the number of Ru ions. The complexes loaded into the nanostructured lipid system maintained in vitro activity and toxicity was found to be reduced compared with the compounds that were not loaded. The complexes showed intra-macrophagic activity and were orally bioavailable

Boron isotope dilution in cellular fractions of coffee leaves Evaluated by Inductively Coupled Plasma Mass Spectrometry with direct injection nebulization (DIN-ICP-MS)

Enriched 10B (94.14 atom %) was supplied to coffee plantlets for three months. Then boron isotope ratios were determined in the leaf cell compartments, cell wall, nuclei and chloroplast, after a sub-cellular fractionation procedure. The isotopic measurements were performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) provided with a direct injection nebulizer (DIN), introducing a sample volume of 50 muL. Isotopic ratios from 1.002 to 1.326 were determined with precision characterized by RSD lower than 1.5% for the enriched cell fractions with B concentrations ranging from 3.3 to 10.8 mug g-1. The detection limit (3sigma) was 0.5 ng B mL-1. The average enrichments in 10B atom % found in the cell walls, nuclei and chloroplasts were 46.7, 44.5 and 48.8, respectively

Residual biomass of coffee as a binding agent in diffusive gradients in thin-films technique for Cd, Cu, Ni, Pb and Zn measurement in waters

Made available in DSpace on 2019-10-06T16:40:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-12-01Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Spent coffee grounds (SCG) immobilized in agarose gel are proposed as a novel binding agent for application in the Diffusive Gradients in Thin films (DGT) technique for the determination of Cd, Cu, Ni, Pb and Zn in waters. The SCG-agarose gel was characterized by Scanning Electron Microscopy, Energy Dispersive X-ray Spectrometry and Porosimetry by nitrogen adsorption. Elution of analytes from the binding agent was effectively performed with 2 mol L−1 HCl. The effects of key DGT parameters (e.g. immersion time, ionic strength and pH) were evaluated with a deployment of DGT devices (DGT-SCG) in synthetic solutions with ionic strengths between 0.005 mol L−1 and 0.1 mol L−1 and within a pH range of 3.5–8.0. The results were in excellent agreement with the predicted theoretical curve for mass uptake. Consistent results were found for solutions with ionic strengths between 0.005 mol L−1 and 0.1 mol L−1 and within a pH range of 3.5–8.0. The DGT-SCG performance was also evaluated in two spiked river water samples (Corumbataí and Piracicaba river) with satisfactory uptake values (CDGT-SCG/Csol) between 0.74 and 1.53. The proposed DGT-SCG opens opportunities for using residual biomass as binding phase in the DGT technique, showing low costs in production and complying with “green” technology approaches.Universidade Estadual Paulista (Unesp) Instituto de Geociências e Ciências Exatas, Rio Claro, Av. 24 A, 1515Universidade Estadual Paulista (Unesp) Centro de Estudos Ambientais, Rio Claro, Av. 24 A, 1515Queen's University Belfast Institute for Global Food Security School of Biological SciencesUniversidade Estadual Paulista (Unesp) Instituto de Geociências e Ciências Exatas, Rio Claro, Av. 24 A, 1515Universidade Estadual Paulista (Unesp) Centro de Estudos Ambientais, Rio Claro, Av. 24 A, 1515FAPESP: 2016/14227-5FAPESP: 2018/17069-7CNPq: 304849/2016-2CNPq: 403666/2016-

Determination of in situ speciation of manganese in treated acid mine drainage water by using multiple diffusive gradients in thin films devices

Acid mine drainage (AMD) is a serious environmental problem that creates acidic solution with high Mn concentrations. The speciation of residual Mn from AMD after an active treatment involving the addition of a neutralizing agent can reliably evaluate the treatment efficiency and provide knowledge of the Mn species being inputted into the environment. The aim of this study was to evaluate the in situ lability and speciation of Mn using the diffusive gradients in thin films (DGT) technique with treated drainage water from a uranium mine (TAMD). DGT devices with different binding phases (Chelex-100 and P81 and DE81membranes) were used to perform the in situ speciation of Mn. A comparison of the results from deploying DGT in the laboratory and in situ shows that the speciation of Mn in TAMD should be performed in situ. Linear deployment curves (from in situ experiments) indicate that the DGT device containing the Chelex-100 binding phase can be used to evaluate Mn lability in TAMD. The labile Mn fraction (from in situ measurements) obtained using the device containing the Chelex-100 resin ranged from 63 to 81% of the total Mn concentration and, when compared to the speciation obtained using the CHEAQS software, indicated that this device was capable of uptaking the free Mn2+ and a portion of the MnSO4(aq). The values obtained using the DGT technique were compared to those from on site solid phase extraction, and a good agreement was found between the results. The amount of negative Mn species sampled by DE81 device was insignificant (150mgL-1), which take place due to the saturation of binding sites in the P81 membrane. © 2013 Elsevier B.V

DETERMINATION OF TIN IN ENVIRONMENTAL SAMPLES BY ATOMIC FLUORESCENCE SPECTROMETRY

An analytical method to determine tin concentrations in natural samples, by coupling atomic fluorescence spectrometry, hydride generation and flow injection system was developed. The sample digestion procedure and the conditions of hydride generation were fully optimized. The best conditions for the generation of SnH4 were obtained with NaBH4 4% (m v-1) and HCl 0.6 mol L-1. The optimized flow rates were 1.2 mL min-1 for sample, 1.2 mL min-1 for HCl and 1.6 mL min-1 for NaBH4 solution. The sample volume was 500 µL. The best acid volume for digestion of solid samples was stablished to be 3 mL HNO3 + 1 mL HCl. The accuracy of the method was established by the analysis of certified reference materials and by comparative determinations, using inductively coupled optical emission spectrometry. The approach developed was shown to offer a robust method with excellent accuracy and precision for the determination of Sn in environmental samples. Finally, the method was applied to analyse the soil, sediment and water samples, collected in area under anthropogenic activities: processing area of cassiterite in Corumbataí/SP. The obtained data indicated that there was alteration in the natural quality of the environment as a result of the activities developed in that sit