ABSTRACT
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.
Subject(s)
Angiotensin Receptor Antagonists , Nanotubes , Antihypertensive Agents , Boron Compounds , Chromatography, High Pressure Liquid/methods , Humans , Losartan , Methanol , Silicon Dioxide , United States , ValsartanABSTRACT
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.
Subject(s)
Boron Compounds/chemistry , Gadolinium/chemistry , Nanomedicine , Nanotubes/chemistry , Oxides/chemistry , Samarium/chemistry , Cell Line , HumansABSTRACT
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.
Subject(s)
Bystander Effect/radiation effects , Flufenamic Acid/chemistry , Flufenamic Acid/pharmacology , Nanoparticles/chemistry , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacology , Bystander Effect/drug effects , Cell Line , Fibroblasts/drug effects , Fibroblasts/radiation effects , Gamma Rays/adverse effects , Humans , Materials Testing , Microscopy, Electron, ScanningABSTRACT
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.
