RESUMO

The limitations of silica-based sorbents boosted the development of new extraction phases. In this study, boron nitride nanotubes functionalized with octadecyl groups were used for the first time as sorbent for extraction of losartan and valsartan, the most used angiotensin receptor blockers in the clinical practice, from human plasma. The nanotubes were synthesized using the chemical vapor deposition technique, purified by acid treatment, functionalized with octadecylamine in a microwave reactor, and characterized by different techniques. The functionalized nanotubes were packed in solid phase extraction cartridges. Extraction conditions were optimized by means of a 23 factorial design with center points. The separation was performed on a biphenyl core-shell (100 × 4.6 mm; 2.6 µm) column, using 0.1 % (v/v) triethylamine solution and methanol (pH 3.2) as mobile phase, at 0.7 mL/min, in gradient elution. The injection volume was 10 µL and fluorescence detection was performed at excitation and emission wavelengths of 250 and 375 nm, respectively. The developed method was validated according to Brazilian Health Regulatory Agency (ANVISA), United States Food and Drug Administration (US FDA) and European Medicines Agency (EMA) guidelines and presented selectivity, precision, accuracy, and linearity in the concentration ranges of 50-1200 ng/mL for losartan and 20-1700 ng/mL for valsartan. Recoveries higher than 80 % were obtained. The method was fit for the quantification of losartan in plasma samples from patients under antihypertensive therapy, being useful in therapeutic drug monitoring, pharmacokinetics and bioequivalence studies.

Assuntos

RESUMO

In this work, the radioisotope 64Cu was obtained from copper (II) chloride dihydrate in a nuclear research reactor by neutron capture, (63Cu(n,γ)64Cu), and incorporated into boron nitride nanotubes (BNNTs) using a solvothermal process. The produced 64Cu-BNNTs were analyzed by TEM, MEV, FTIR, XDR, XPS and gamma spectrometry, with which it was possible to observe the formation of64Cu nanoparticles, with sizes of up to 16 nm, distributed through nanotubes. The synthesized of 64Cu nanostructures showed a pure photoemission peak of 511 keV, which is characteristic of gamma radiation. This type of emission is desirable for Photon Emission Tomography (PET scan) image acquisition, as well as its use in several cancer treatments. Thus, 64Cu-BNNTs present an excellent alternative as theranostic nanomaterials that can be used in diagnosis and therapy by different techniques used in nuclear medicine.

RESUMO

The detailed study of graphene oxide (GO) synthesis by changing the graphite/oxidizing reagents mass ratios (mG/mROxi), provided GO nanosheets production with good yield, structural quality, and process savings. Three initial samples containing different amounts of graphite (3.0 g, 4.5 g, and 6.0 g) were produced using a bench reactor under strictly controlled conditions to guarantee the process reproducibility. The produced samples were analyzed by Raman spectroscopy, atomic force microscopy (AFM), x-ray diffraction (XDR), X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FTIR) and thermogravimetry (TGA) techniques. The results showed that the major GO product comprised of nanosheets containing between 1-5 layers, with lateral size up to 1.8 µm. Therefore, it was possible to produce different batches of graphene oxide with desirable physicochemical characteristics, keeping the amount of oxidizing reagent unchanged. The use of different proportions (mG/mROxi) is an important strategy that provides to produce GO nanostructures with high structural quality and scale-up, which can be well adapted in medium-sized bench reactor.

RESUMO

Boron nitride nanotubes (BNNTs) have been growing in notoriety in the development of systems aiming bioapplications. In this work we conducted an investigation about the mechanisms involved in the incorporation of samarium and gadolinium in BNNTs. The process was performed by the reduction of samarium and gadolinium oxides (Sm2O3 and Gd2O3, respectively) in the presence of NH3 gas (witch decomposes into N2 and H2) at high temperatures. Various characterization techniques were conducted to elucidate how Sm and Gd are introduced into the BNNT structure. Biological in vitro assays were performed with human fibroblasts and a human osteosarcoma cell line (SAOS-2). Our results show that the studied systems have high potential for biomedical application and can be used as non-invasive imaging agents, such as scintigraphy radiotracers or as magnetic resonance imaging (MRI) contrast medium, being able to promote the treatment of many types of tumors simultaneously to their diagnosis.

Assuntos

RESUMO

The development of a myriad of nanoparticles types has opened new possibilities for the diagnostics and treatment of many diseases, especially for cancer. However, most of the researches done so far do not focus on the protection of normal cells surrounding a tumor from irradiation bystander effects that might lead to cancer recurrence. Gap-junctions are known to be involved in this process, which leads to genomic instability of neighboring normal cells, and flufenamic acid (FFA) is included in a new group of gap-junction blockers recently discovered. The present work explores the use of mesoporous silica nanoparticles MCM-41 functionalized with 3-Aminopropyltriethoxysilane (APTES) for anchoring the flufenamic acid for its prolonged and controlled release and protection from radiation bystander effects. MCM-41 and functionalized samples were structurally and chemically characterized with multiple techniques. The biocompatibility of all samples was tested in a live/dead assay performed in cultured MRC-5 and HeLa cells. HeLa cells cultured were exposed to 50 Gy of gamma-rays and the media transferred to fibroblast cells cultured separately. Our results show that MCM-41 and functionalized samples have high biocompatibility with MCR-5 and HeLa cells, and most importantly, the FFA delivered by these NPs was able to halt apoptosis, one of main bystander effects.

Assuntos

RESUMO

Recently, flufenamic acid (FFA) was discovered among fenamates as a free radical scavenger and gap junction blocker; however, its effects have only been studied in cancer cells. Normal cells in the surroundings of a tumor also respond to radiation, although they are not hit by it directly. This phenomenon is known as the bystander effect, where response molecules pass from tumor cells to normal ones, through communication channels called gap junctions. The use of the enhanced permeability and retention effect, through which drug-loaded nanoparticles smaller than 200 nm may accumulate around a tumor, can prevent the local side effect upon controlled release of the drug. The present work, aimed at functionalizing MCM-41 (Mobil Composition of Matter No. 41) silica nanoparticles with FFA and determining its biocompatibility with human fibroblasts MRC-5 (Medical Research Council cell strain 5). MCM-41, was synthesized and characterized structurally and chemically, with multiple techniques. The biocompatibility assay was performed by Live/Dead technique, with calcein and propidium-iodide. MRC-5 cells were treated with FFA-grafted MCM-41 for 48 h, and 98% of cells remained viable, without signs of necrosis or morphological changes. The results show the feasibility of MCM-41 functionalization with FFA, and its potential protection of normal cells, in comparison to the role of FFA in cancerous ones.

RESUMO

Boron nitride nanotubes doped in situ with samarium (Sm-doped BNNTs) were synthesized at 1150°C under atmosphere of NH3/N2 gas mixture by thermal chemical vapor deposition (TCVD) using samarium oxide that is a product of the process separation of thorium and uranium tailings. The samarium in the BNNTs sample was activated by neutron capture, in a nuclear reactor, producing 152Sm radioisotopes. The STEM-EELS spectrum and neutron activation show energies attributed to the samarium confirming the in situ doping process during BNNTs growth. The results demonstrate that this material has great potential as a nanosized ß- emission source for medical therapy.