Co-delivery of buparvaquone and polymyxin B in a nanostructured lipid carrier for leishmaniasis treatment

Objectives: This study aimed to describe the preparation and in vitro evaluation of a surface-modified nanostructured lipid carrier (NLC) using chitosan and dextran for co-delivery of buparvaquone (BPQ) and polymyxin B (PB) against leishmaniasis. Methods: The NLC was prepared using high-pressure homogenisation. Polymyxin B binding and surface modification with biopolymers were achieved by electrostatic interaction. In vitro cytotoxicity was assessed in mouse peritoneal macrophages, and leishmanicidal activity in amastigotes of Leishmania infantum. Results: The performance attributes of BPQ-NLC, BPQ-NLC-PB[A −] (anionic) and BPQ-NLC-PB[C +] (cationic) were respectively: Z-average 173.9 ± 1.6, 183.8 ± 4.5 and 208.8 ± 2.6 nm; zeta potential −19.6 ± 1.5, −20.1 ± 1.1 and 31.1 ± 0.8 mV; CC 50 583.4 ± 0.10, 203.1 ± 0.04 and 5.7 ± 0.06 μM; IC 50 229.0 ± 0.04, 145.7 ± 0.04 and 150.5 ± 0.02 nM. The NLC in vitro leishmanicidal activity showed up to 3.1-fold increase when compared with free BPQ (P &lt; 0.05, α = 0.05). Conclusions: The developed NLC proved to be a promising formulation with which to overcome the drawbacks of current leishmaniasis treatment by the co-delivery of two alternative drugs and a macrophage targeting modified surface. </p

Magnetic hyperthermia experiments with magnetic nanoparticles in clarified butter oil and paraffin: A thermodynamic analysis

In specific power absorption models for magnetic fluid hyperthermia (MFH) experiments, the magnetic relaxation time of nanoparticles (NPs) is known to be a fundamental descriptor of the heating mechanisms. The relaxation time is mainly determined by the interplay between the magnetic properties of NPs and the rheological properties of NPs’ environment. Although the role of magnetism in MFH has been extensively studied, the thermal properties of the NP medium and their changes during MFH experiments have been underrated so far. Herein, we show that ZnxFe3-xO4 NPs dispersed through different media with phase transition in the temperature range of experiment as clarified butter oil (CBO) and paraffin. These systems show nonlinear behavior of the heating rate within the temperature range of MFH experiments. For CBO, a fast increase at ~306 K is associated with changes in the viscosity (¿(T)) and specific heat (cp(T)) of the medium at its melting temperature. This increment in the heating rate takes place around 318 K for paraffin. The magnetic and morphological characterization of NPs together with the observed agglomeration of NPs above 306 and 318 K for CBO and paraffin, respectively, indicate that the fast increase in MFH curves could not be associated with the change in the magnetic relaxation mechanism, with Neél relaxation being dominant. In fact, successive experimental runs performed up to temperatures below and above the CBO and paraffin melting points resulted in different MFH curves due to agglomeration of NPs driven by magnetic field inhomogeneity during the experiments. Our results highlight the relevance of the thermodynamic properties of the system NP-medium for an accurate measurement of the heating efficiency for in vitro and in vivo environments, where the thermal properties are largely variable within the temperature window of MFH experiments

Walking training improves systemic and local pathophysiological processes in intermittent claudication

Objective: This study examined the impact of submaximal walking training (WT) on local and systemic nitric oxide (NO) bioavailability, inflammation, and oxidative stress in patients with intermittent claudication (IC). Methods: The study employed a randomised, controlled, parallel group design and was performed in a single centre. Thirty-two men with IC were randomly allocated to two groups: WT (n = 16, two sessions/week, 15 cycles of two minutes walking at an intensity corresponding to the heart rate obtained at the pain threshold interspersed by two minutes of upright rest) and control (CO, n = 16, two sessions/week, 30 minutes of stretching). NO bioavailability (blood NO and muscle nitric oxide synthase [eNOS]), redox homeostasis (catalase [CAT], superoxide dismutase [SOD], lipid peroxidation [LPO] measured in blood and muscle), and inflammation (interleukin-6 [IL-6], C-reactive protein [CRP], tumour necrosis factor α [TNF-α], intercellular adhesion molecules [ICAM], vascular adhesion molecules [VCAM] measured in blood and muscle) were assessed at baseline and after 12 weeks. Results: WT statistically significantly increased blood NO, muscle eNOS, blood SOD and CAT, and muscle SOD and abolished the increase in circulating and muscle LPO observed in the CO group. WT decreased blood CRP, ICAM, and VCAM and muscle IL-6 and CRP and eliminated the increase in blood TNF-α and muscle TNF-α, ICAM and VCAM observed in the CO group. Conclusion: WT at an intensity of pain threshold improved NO bioavailability and decreased systemic and local oxidative stress and inflammation in patients with IC. The proposed WT protocol provides physiological adaptations that may contribute to cardiovascular health in these patients

Adjusting the Neel relaxation time of Fe3O4/ZnxCo1-xFe2O4 core/shell nanoparticles for optimal heat generation in magnetic hyperthermia

In this work it is shown a precise way to optimize the heat generation in high viscosity magnetic colloids, by adjusting the Neel relaxation time in core/shell bimagnetic nanoparticles, for magnetic fluid hyperthermia (MFH) applications. To pursue this goal, Fe3O4/ZnxCo1-xFe2O4 core/shell nanoparticles were synthesized with 8.5 nm mean core diameter, encapsulated in a shell of similar to 1.1 nm of thickness, where the Zn atomic ratio (Zn/(Zn + Co) at%) changes from 33 to 68 at%. The magnetic measurements are consistent with a rigid interface coupling between the core and shell phases, where the effective magnetic anisotropy systematically decreases when the Zn concentration increases, without a significant change of the saturation magnetization. Experiments of MFH of 0.1 wt% of these particles dispersed in water, in Dulbecco modified Eagles minimal essential medium, and a high viscosity butter oil, result in a large specific loss power (SLP), up to 150 W g(-1), when the experiments are performed at 571 kHz and 200 Oe. The SLP was optimized adjusting the shell composition, showing a maximum for intermediate Zn concentration. This study shows a way to maximize the heat generation in viscous media like cytosol, for those biomedical applications that require smaller particle sizes

Unusual magnetic relaxation behavior in La0.5Ca0.5MnO3 and Nd0.5Sr0.5MnO3

We have carried out a systematic magnetic relaxation study, measured after applying and switching off a 5 T magnetic field to polycrystalline samples of La0.5Ca0.5MnO3 and Nd0.5Sr0.5MnO3. The long time logarithmic relaxation rate (LTLRR), decreased from 10 K to 150 K and increased from 150 K to 195 K in La0.5Ca0.5MnO3. This change in behavior was found to be related to the complete suppression of the antiferromagnetic phase above 150 K and in the presence of a 5 T magnetic field. At 195 K, the magnetization first decreased, and after a few minutes increased slowly as a function of time. Moreover, between 200 K and 245 K, the magnetization increased throughout the measured time span. The change in the slope of the curves, from negative to positive at about 200 K was found to be related to the suppression of antiferromagnetic fluctuations in small magnetic fields. A similar temperature dependence of the LTLRR was found for the Nd0.5Sr0.5MnO3 sample. However, the temperature where the LTLRR reached the minimum in Nd0.5Sr0.5MnO3 was lower than that of La0.5Ca0.5MnO3. This result agrees with the stronger ferromagnetic interactions that exist in Nd0.5Sr0.5MnO3 in comparison to La0.5Ca0.5MnO3. The above measurements suggested that the general temperature dependence of the LTLRR and the underlying physics were mainly independent of the particular charge ordering system considered. All relaxation curves could be fitted using a logarithmic law at long times. This slow relaxation was attributed to the coexistence of ferromagnetic and antiferromagnetic interactions between Mn ions, which produced a distribution of energy barriers.Comment: Accepted to PRB as a regular article, 10 figures, Scheduled Issue: 01 June 200

Effects of Zn Substitution in the Magnetic and Morphological Properties of Fe-Oxide-Based Core-Shell Nanoparticles Produced in a Single Chemical Synthesis

Magnetic, compositional, and morphological properties of Zn-Fe-oxide core-shell bimagnetic nanoparticles were studied for three samples with 0.00, 0.06, and 0.10 Zn/Fe ratios, as obtained from particle-induced X-ray emission analysis. The bimagnetic nanoparticles were produced in a one-step synthesis by the thermal decomposition of the respective acetylacetonates. The nanoparticles present an average particle size between 25 and 30 nm as inferred from transmission electron microscopy (TEM). High-resolution TEM images clearly show core-shell morphology for the particles in all samples. The core is composed by an antiferromagnetic (AFM) phase with a Wüstite (Fe1-yO) structure, whereas the shell is composed by a ZnxFe3-xO4 ferrimagnetic (FiM) spinel phase. Despite the low solubility of Zn in the Wüstite, electron energy-loss spectroscopy analysis indicates that Zn is distributed almost homogeneously in the whole nanoparticle. This result gives information on the formation mechanisms of the particle, indicating that the Wüstite is formed first, and the superficial oxidation results in the FiM ferrite phase with similar Zn concentration than the core. Magnetization and in-field Mössbauer spectroscopy of the Zn-richest nanoparticles indicate that the AFM phase is strongly coupled to the FiM structure of the ferrite shell, resulting in a bias field (HEB) appearing below TNFeO, with HEB values that depend on the core-shell relative proportion. Magnetic characterization also indicates a strong magnetic frustration for the samples with higher Zn concentration, even at low temperatures

Low-intensity resistance exercise does not affect cardiac autonomic modulation in patients with peripheral artery disease

OBJECTIVE: To analyze the effect of a single bout of resistance exercise on cardiac autonomic modulation in patients with peripheral artery disease. METHODS: Fifteen patients with peripheral artery disease (age: 58.3±4.0 years) underwent the following sessions in a random order: resistance exercise (three sets of 10 repetitions of the six resistance exercises with a workload of 5-7 in the OMNI-RES scale) and control (similar to the resistance session; however, the resistance exercises were performed with no load). The frequency domain (low frequency, high frequency and sympathovagal balance) and symbolic analysis (0V, 1V and 2V patterns) of heart rate variability were obtained before and until one hour after the interventions. RESULTS: After the resistance exercise and control sessions, similar increases were observed in the consecutive heartbeat intervals (control: 720.8±28.6 vs. 790.9±34.4 ms; resistance exercise: 712.9±30.1 vs. 756.8±37.9 ms;

Sensor based on β - NiOx hybrid film/multi-walled carbon nanotubes composite electrode for groundwater salinization inspection

The enrichment of groundwater with different nutrients (Na+, Ca2+, Mg2+, Cl−, CO32−, among others) triggers the salinization of the aquifer and makes it inappropriate for many purposes. In this work, we developed a highly sensitive and selective electrochemical sensor, based on Ni-inorganic films electrosynthetized in situ onto multi-walled carbon nanotubes composite paste electrode (MWCNE), which allows the early detection of salinization. The working sensor (β-NiOx/MWCNE) was derivatized from nickel hexacyanoferrate modified electrode in strong alkaline medium (pH = 12), producing a hybrid film composed by β-Ni(OH)2 and β-NiO(OH). The electrochemical properties, morphology and chemical composition of the formed β-NiOx thin films were evaluated by voltammetry, scanning electron microscopy and X-ray spectroscopy. The developed β-NiOx/MWCNE sensor was highly sensitive to the presence of Na+ cation by ion-exchange, and the increase of Na+ concentration in the range 4.46 × 10−7 to 4.93 × 10−6 mol L−1 inhibited linearly the reversible electrochemical signal of the device, allowing to determine trace concentrations of this ion (LOD = 9.86 × 10−8 mol L−1) with high correlation coefficient of the data (r = 0.999) and suitable precision/reproducibility of the measurements (RSD < 9%). Using Na+ as salinization marker and β-NiOx/MWCNE as electroanalytical device, we found evidences of groundwater salinization in Grossos, a Brazil coast city, whose inhabitants have hypertension above the national average. The attained results were comparable to those obtained by the standard methods for Na+ analysis (percentage error ranging from 0.5 to 1.6%), confirming the accuracy of the proposed electroanalytical platform.info:eu-repo/semantics/publishedVersio