Violacein and its antifungal activity: comments and potentialities.

Violacein is an important natural antimicrobial pigment that is mainly produced by Chromobacterium violaceum and Janthinobacterium lividum. It presents a significant range of effects against phytopathogenic and human fungi, besides being featured as having low toxicity, and by its important ecological role in protecting amphibian species and applications in dyed medical fabric. The hypothesis about violacein's action mechanisms against mucormycosis (Rhizopus arrhizus) and candidiasis (Candida auris) is herein discussed based on data available in the scientific literature.

Design of magnetic hybrid nanostructured lipid carriers containing 1,8-cineole as delivery systems for anticancer drugs: Physicochemical and cytotoxic studies.

The development of versatile carriers to deliver chemotherapeutic agents to specific targets with establishing drug release kinetics and minimum undesirable side effects is becoming a promising relevant tool in the medical field. Magnetic hybrid nanostructured lipid carriers (NLC) were prepared by incorporation of 1,8-cineole (CN, a monoterpene with antiproliferative properties) and maghemite nanoparticles (MNPs) into a hybrid matrix composed of myristyl myristate coated with chitosan. Hybrid NLC characterized by DLS and TEM confirmed the presence of positively charged spherical nanoparticles of around 250 nm diameter and +10.2 mV of Z-potential. CN encapsulation into the lipid core was greater than 75 % and effectively released in 24 h. Modification of the crystalline structure of nanoparticles after incorporation of CN and MNPs was observed by XRD, DSC, and TGA analyses. Superparamagnetic NLC behavior was verified by recording the magnetization using a vibrating scanning magnetometer. NLC resulted in more cytotoxic than free CN in HepG2 and A549 cell lines. Particularly, viability inhibition of HepG2 and A549 cells was increased from 35 % to 55 % and from 38 % to 61 %, respectively, when 8 mM CN was incorporated into the lipid NPs at 24 h. Green fluorescent-labeled NLC with DIOC18 showed an enhanced cellular uptake with chitosan-coated NLC. Besides, no cytotoxicity of the formulations in normal WI-38 cells was observed, suggesting that the developed hybrid NLC system is a safe and good potential candidate for the selective delivery and potentiation of anticancer drugs.

Nutritional value and antioxidant compounds during the ripening and after domestic cooking of bananas and plantains.

Genotypes of bananas and plantains have been studied for biofortification purposes, mainly due to content of resistant starch (RS) and polyphenols. This study aims to identify banana and plantain genotypes with a high content of resistant starch, phenolic compounds and minerals, and to evaluate the impact of the ripening stage and domestic thermal processing to select superior genotypes with high levels of functional compounds. In this study, it was used bunches of bananas and plantain genotypes. The phenolic compounds profiles were determined by HPLC-DAD in pulps and peels. The resistant starch and the minerals (K, Na, Zn, Cu and Fe) were evaluated in pulps and peels of unripe fruit. The results of phenolic compounds were studied in three ripening stages, and after thermal processing (ripe stage) of two genotypes, which were most promising for biofortification studies. Resistant starch and minerals were analysed in the unripe fruits. The peel biomass showed the highest values of phenolic compounds and minerals. The total starch content in the pulp varied from 42.3% ('FC06-02') to 80.6% ('Pelipita'). Plantains and cooking bananas presented the highest contents of starch and resistant starch (stage 2 - green with yellow traces). The pulps of the dessert genotypes 'Khai' and 'Ouro da Mata', and cooking genotype 'Pacha Nadam' stood out due to their minerals high contents (P, K and Fe; Zn and Fe; Ca, Mg and Zn, respectively). The dessert bananas (e.g., 'Ney Poovan') and cooking bananas (e.g., 'Tiparot') had the highest concentrations of phenolic compounds, mainly in ripe fruit (stage 5 - yellow with green). In addition, the thermal processing of Musa spp. fruit led to increasing these secondary metabolites, mainly the cooking of fruit with peel by boiling, which should be preferred in domestic preparations.

Hybrid Ofloxacin/eugenol co-loaded solid lipid nanoparticles with enhanced and targetable antimicrobial properties.

In the global context of an imminent emergence of multidrug-resistant microorganisms, the present work combined the use of nanotechnology and the therapeutic benefits of natural compounds as a strategy to potentiate antimicrobial action of the wide-spectrum antibiotic Ofloxacin (Ofx). Hybrid solid lipid nanoparticles (SLN) were synthesized by incorporation of chitosan (Chi, a cationic biopolymer with antimicrobial activity) and eugenol (Eu, a phenolic compound that interferes with bacterial quorum sensing) into a lipid matrix by hot homogenization/ultrasonication method. The developed SLN/Chi/Eu sustainably released the encapsulated Ofx for 24 h. Characterization by DLS, TEM, DSC, TGA and XRD revealed the presence of positively charged spherical nanoparticles with diameters around 300 nm and Ofx entrapped in amorphous state. The SLN exhibited an enhanced bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration (MIC) for free and nanoencapsulated Ofx formulations was below 1.0 µg/ml. The MIC values decreased by 6.1- to 16.1-fold when Ofx was encapsulated in SLN/Chi/Eu. Fluorescent-labeled nanoparticles had the ability to interact with the bacterial cell membrane. Selective toxicity of SLN/Chi/Eu-Ofx was tested in the range of 0.3-30.0 µg/ml and showed no toxicity up to 3.0 µg/ml Ofx in human cell models (A549 and Wi-38) at 24 h and 48 h exposure. It was proved that the administration of hybrid SLN to mice by dry powder inhalation reached therapeutic Ofx levels in lungs.

Self-assembly of iron oxide precursor micelles driven by magnetic stirring time in sol-gel coatings.

The purpose of this work is to fabricate self-assembled microstructures by the sol-gel method and study the morphological, structural and compositional dependence of ε-Fe2O3 nanoparticles embedded in silica when glycerol (GLY) and cetyl-trimethylammonium bromide (CTAB) are added as steric agents simultaneously. The combined action of a polyalcohol and a surfactant significantly modifies the morphology of the sample giving rise to a different microstructure in each of the studied cases (1, 3 and 7 days of magnetic stirring time). This is due to the fact that the addition of these two compounds leads to a considerable increase in gelation time as GLY can interact with the alkoxide group on the surface of the iron oxide precursor micelle and/or be incorporated into the hydrophilic chains of CTAB. This last effect causes the iron oxide precursor micelles to be interconnected forming aggregates whose size and structure depend on the magnetic stirring time of the sol-gel synthetic route. In this paper, crystalline structure, composition, purity and morphology of the sol-gel coatings densified at 960 °C are examined. Emphasis is placed on the nominal percentage of the different iron oxides found in the samples and on the morphological and structural differences. This work implies the possibility of patterning ε-Fe2O3 nanoparticles in coatings and controlling their purity by an easy one-pot sol-gel method.

Bacterial cellulose hydrogel loaded with lipid nanoparticles for localized cancer treatment.

The use of hybrid materials, where a matrix sustains nanoparticles controlling the release of the chemotherapeutic drug, could be beneficial for the treatment of primary tumors prior or after surgery. This localized chemotherapy would guarantee high drug concentrations at the tumor site while precluding systemic drug exposure minimizing undesirable side effects. We combined bacterial cellulose hydrogel (BC) and nanostructured lipid carriers (NLCs) including doxorubicin (Dox) as a drug model. NLCs loaded with cationic Dox (NLCs-H) or neutral Dox (NLCs-N) were fully characterized and their cell internalization and cytotoxic efficacy were evaluated in vitro against MDA-MB-231 cells. Thereafter, a fixed combination of NLCs-H and NLCs-N loaded into BC (BC-NLCs-NH) was assayed in vivo into an orthotopic breast cancer mouse model. NLCs-H showed low encapsulation efficiency (48%) and fast release of the drug while NLCs-N showed higher encapsulation (97%) and sustained drug release. Both NLCs internalized via endocytic pathway, while allowing a sustained release of the Dox, which in turn rendered IC50 values below of those of free Dox. Taking advantage of the differential drug release, a mixture of NLCs-N and NLCs-H was encapsulated into BC matrix (BC-NLCs-NH) and assayed in vivo, showing a significant reduction of tumor growth, metastasis incidence and local drug toxicities.

Carbamazepine-loaded solid lipid nanoparticles and nanostructured lipid carriers: Physicochemical characterization and in vitro/in vivo evaluation.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) represent promising alternatives for drug delivery to the central nervous system. In the present work, four different nanoformulations of the antiepileptic drug Carbamazepine (CBZ) were designed and prepared by the homogenization/ultrasonication method, with encapsulation efficiencies ranging from 82.8 to 93.8%. The formulations remained stable at 4 °C for at least 3 months. Physicochemical and microscopic characterization were performed by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), atomic force microscopy (AFM); thermal properties by differential scanning calorimetry (DSC), thermogravimetry (TGA) and X-ray diffraction analysis (XRD). The results indicated the presence of spherical shape nanoparticles with a mean particle diameter around 160 nm in a narrow size distribution; the entrapped CBZ displayed an amorphous state. The in vitro release profile of CBZ fitted into a Baker-Lonsdale model for spherical matrices and almost the 100% of the encapsulated drug was released in a controlled manner during the first 24 h. The apparent permeability of CBZ-loaded nanoparticles through a cell monolayer model was similar to that of the free drug. In vivo experiments in a mice model of seizure suggested protection by CBZ-NLC against seizures for at least 2 h after intraperitoneal administration. The developed CBZ-loaded lipid nanocarriers displayed optimal characteristics of size, shape and drug release and possibly represent a promising tool to improve the treatment of refractory epilepsy linked to efflux transporters upregulation.

Origin of the magnetic transition at 100 K in ε-Fe2O3 nanoparticles studied by x-ray absorption fine structure spectroscopy.

The current study unveils the structural origin of the magnetic transition of the ε-Fe2O3 polymorph from an incommensurate magnetic order to a collinear ferrimagnetic state at low temperature. The high crystallinity of the samples and the absence of other iron oxide polymorphs have allowed us to carry out temperature-dependent x-ray absorption fine structure spectroscopy experiments out. The deformation of the structure is followed by the Debye-Waller factor for each selected Fe-O and Fe-Fe sub-shell. For nanoparticle sizes between 7 and 15 nm, the structural distortions between the Fete and Fe-D1oc sites are localized in a temperature range before the magnetic transition starts. On the contrary, the inherent interaction between the other sub-shells (named Fe-O1,2 and Fe-Fe1) provokes cooperative magneto-structural changes in the same temperature range. This means that the Fete with Fe-D1oc polyhedron interaction seems to be uncoupled with temperature dealing with these nanoparticle sizes wherein the structural distortions are likely moderate due to surface effects.

Hybrid inhalable microparticles for dual controlled release of levofloxacin and DNase: physicochemical characterization and in vivo targeted delivery to the lungs.

Current medical treatments against recurrent pulmonary infections caused by Pseudomonas aeruginosa, such as cystic fibrosis (CF) disorder, involve the administration of inhalable antibiotics. The main challenge is, however, the eradication of microbial biofilms immersed in dense mucus that requires high and recurrent antibiotic doses. Accordingly, the development of novel drug delivery systems capable of providing local and controlled drug release in the lungs is a key factor to improve the therapeutic outcome of such therapeutic molecules. Inhalable hybrid carriers were prepared by co-precipitation of CaCO3 in the presence of alginate and the resulting microparticles were treated with alginate lyase (AL) in order to modify their porosity and enhance the drug loading. The hybrid microparticles were loaded with DNase (mucolytic agent) and levofloxacin (LV, wide-spectrum antibiotic) in the range of 20-40% for LV and 28-67% for DNase, depending on the AL treatment. In vitro studies demonstrated that microparticles were able to control the DNase release for 24 h, while 30-50% of LV was released in 3 days. The morphological characterization was performed by optical, fluorescence and scanning electron microscopies, showing a narrow size distribution (5 µm). FTIR, XRD, DSC and nitrogen adsorption isotherm studies revealed the presence of the drugs in a non-crystalline state. A microcidal effect of microparticles was found on P. aeruginosa in agar plates and corroborated by Live/Dead kit and TEM observations. Finally, to study whether the microparticles improved the localization of LV in the lungs, in vivo studies were performed by pulmonary administration of microparticles to healthy mice via nebulization and dry powder inhalation, followed by the quantification of LV in lung tissue. The results showed that microparticles loaded with LV delivered the antibiotic at least 3 times more efficiently than free LV. The developed system opens the gateway to new drug delivery systems that may provide enhanced therapeutic solutions against bacterial infections and in particular as a potential tool in CF pathology.

Formation of titanium monoxide (001) single-crystalline thin film induced by ion bombardment of titanium dioxide (110).

A plethora of technological applications justify why titanium dioxide is probably the most studied oxide, and an optimal exploitation of its properties quite frequently requires a controlled modification of the surface. Low-energy ion bombardment is one of the most extended techniques for this purpose and has been recently used in titanium oxides, among other applications, to favour resistive switching mechanisms or to form transparent conductive layers. Surfaces modified in this way are frequently described as reduced and defective, with a high density of oxygen vacancies. Here we show, at variance with this view, that high ion doses on rutile titanium dioxide (110) induce its transformation into a nanometric and single-crystalline titanium monoxide (001) thin film with rocksalt structure. The discovery of this ability may pave the way to new technical applications of ion bombardment not previously reported, which can be used to fabricate heterostructures and interfaces.

Development and characterization of new enzymatic modified hybrid calcium carbonate microparticles to obtain nano-architectured surfaces for enhanced drug loading.

HYPOTHESIS: Biopolymer-CaCO3 hybrid microparticles exposed to hydrolytic enzymes can provide new surface tailorable architectures. Soluble Alginate Lyase hydrolyzed alginate chains exposed on microparticle surface are generating considerable matrix changes. The change of porosity and surface to volume ratio is expected to influence absorption of drugs, thereby affecting controlled release profiles. The developed hybrid system potentially shows interesting properties for lung drug administration. EXPERIMENTAL: Hybrid microparticles were developed by colloidal co-precipitation of CaCO3 in presence of biopolymers: alginate (Alg) or Alg-High Methoxylated Pectin (HMP), followed by treatment with Alginate Lyase (AL). Surface architectures were observed by SEM. The increase in area to volume ratio was confirmed by BET isotherms. Also, enzymatic changes were elucidated by biophysical methods (EDAX, DSC, FTIR, XRD) and determination of the total carbohydrates content. Levofloxacin (a fluoroquinolone antibiotic) as model drug was incorporated by absorption. The drug release profile and the antimicrobial activity of the microparticles were tested against Pseudomonas aeruginosa. FINDINGS: After enzyme treatment, microspheres showed 4µm diameter and increased porosity. While CaCO3-Alg microspheres resulted in a rougher surface, CaCO3-Alg-HMP ones exhibited "nano-balloon" patterns on surface. Both AL-treated microparticles showed up to 3 and 7 times higher Levofloxacin encapsulation than no treated ones. Microparticles showed controlled drug release profiles and enhanced antimicrobial effect. The present work demonstrates a significant progress in the development of new carriers with potential application for lung infections treatment.

Environmental influence on Zn-histidine complexes under no-packing conditions.

This paper describes a combined structural analysis of the Zn-histidine complex, using two different and complementary techniques, X-ray absorption spectroscopy (XAS) and surface X-ray diffraction, paying special attention to the environmental conditions. The current procedure for investigating macromolecules consists of examining simple molecules that exhibit properties similar to those of the larger ones, whose functionality is totally related to the atomic structure. The detailed study of the bonding structure formed by zinc and histidine amino acids is motivated by the fact that this material serves as a model for metalloproteins, such as in metalloproteinase, acting as active sites in enzymatic or structural functions. For XAS modeling, Zn-histidine complexes were dissolved in several aqueous solutions, over a wide pH range. Correlations among the degree of protonation, the steric impediment, and the multiple combinations of the histidine amino acid have been found. For the diffraction study, high-quality crystals grown by the seeding method in a supersaturated solution have been studied, and the samples for the surface diffraction study were mounted on a cell specially designed for solid-liquid or solid-gas interface analysis. The surface structural model was built from XAS results. In both cases, the obtained structures are compared with the bulk one, showing atomic differences and highlighting the importance of the environment in which the complex is studied.

Surface octahedral distortions and atomic design of perovskite interfaces.

Atomic engineering of perovskite films and interfaces is significantly improved by in situ optimization of reflection high-energy electron diffraction (RHEED) features resulting from surface BO6 octahedral rotations seen during molecular-beam epitaxy growth. This approach yields Sr-doped manganite films across the phase diagram with magnetotransport properties that are, for the first time, identical to bulk single crystals. Careful structural analysis of manganite/titanate interfaces shows that cation intermixing and unit cell dilations are eliminated, while BO6 rotations and Jahn-Teller-type elongations are nearly completely suppressed at the interface.

Photoemission spectroscopy study of the lanthanum lutetium oxide/silicon interface.

Rare earth oxides are promising candidates for future integration into nano-electronics. A key property of these oxides is their ability to form silicates in order to replace the interfacial layer in Si-based complementary metal-oxide field effect transistors. In this work a detailed study of lanthanum lutetium oxide based gate stacks is presented. Special attention is given to the silicate formation at temperatures typical for CMOS processing. The experimental analysis is based on hard x-ray photoemission spectroscopy complemented by standard laboratory experiments as Rutherford backscattering spectrometry and high-resolution transmission electron microscopy. Homogenously distributed La silicate and Lu silicate at the Si interface are proven to form already during gate oxide deposition. During the thermal treatment Si atoms diffuse through the oxide layer towards the TiN metal gate. This mechanism is identified to be promoted via Lu-O bonds, whereby the diffusion of La was found to be less important.

Simultaneous surface plasmon resonance and x-ray absorption spectroscopy.

We present an experimental setup for the simultaneous measurement of surface plasmon resonance (SPR) and x-ray absorption spectroscopy (XAS) on metallic thin films at a synchrotron beamline. The system allows measuring in situ and in real time the effect of x-ray irradiation on the SPR curves to explore the interaction of x-rays with matter. It is also possible to record XAS spectra while exciting SPR in order to study changes in the films induced by the excitation of surface plasmons. Combined experiments recording simultaneously SPR and XAS curves while scanning different parameters can be also carried out. The relative variations in the SPR and XAS spectra that can be detected with this setup range from 10(-3) to 10(-5), depending on the particular experiment.

High Voltage-Cylinder Sector Analyzer 300/15: a cylindrical sector analyzer for electron kinetic energies up to 15 keV.

We have developed an energy analyzer, High Voltage-Cylinder Sector Analyzer 300/15, for electron kinetic energies up to 15 keV. It is especially suited for hard x-ray photoelectron spectroscopy, but also for ultraviolet and soft x-ray photoelectron spectroscopy (ultraviolet photoemission spectroscopy, x-ray photoemission spectroscopy), Auger electron spectroscopy, and reflection high energy electron spectroscopy. The analyzer is based on a cylinder sector with 90 degrees deflection, 300 mm slit-to-slit distance, and a four-element pre-retarding lens system with 50 mm sample-to-lens distance. The result is a very compact design of the analyzer that is easily integrated into a multipurpose experiment with different techniques. A low noise/low drift electronics is capable of continuous energy scans from 0 to 15 keV using nonlinear lens curves. The first analyzer is allocated at the Spanish CRG SpLine beamline at the ESRF at an end station where simultaneous surface x-ray diffraction is possible. The analyzer is operated routinely since 2006 up to 15 keV electron kinetic energy, expanding the achievable electron kinetic energy range compared to other commercial analyzers. In this work we present a detailed description of the developed electron analyzer. The analyzer capabilities, in terms of energy resolution and transmission, are shown by using an electron gun, an ultraviolet-discharge lamp, and hard x-ray synchrotron radiation as excitation sources.

Flare-up of hand osteoarthritis caused by zoledronic acid infusion.

Zoledronic acid is effective for osteoporosis at a single annual intravenous dose. It usually causes few adverse effects; the most common are related to acute phase reactions. We reported the case of a 64-year-old woman who presented flare-up of hand osteoarthritis after zoledronic acid infusions. Despite the fact that arthralgia is a common side effect of intravenous bisphosphonates, development of inflammatory signs in osteoarthritic joints is a rare event. We hypothesized that this side effect is caused by a release of cytokines secondary to activation of gamma-delta T lymphocytes.

Preconcentration and determination of Cu(II) in a fresh water sample using modified silica gel as a solid-phase extraction adsorbent.

A method was developed to attach 4-amino-2-mercaptopyrimidine (AMP) onto silica gel surface and to determine trace metals. The surface functionalization reaction was performed with a silylant agent, chloropropyltrimethoxysilane (Si-CPTS), and the product, Si-AMP, was characterized by FT-IR and elemental analysis to evaluate the surface modification. The functionalized silica was applied in the sorption of Cu(II) ions from an aqueous medium. The series of adsorption isotherms were adjusted to a modified Langmuir equation and the maximum number of moles of adsorbed copper was 0.447 mmol g(-1). The modified material was placed in a preconcentration system, where it reached an approximately 20-fold enrichment factor using 5mg of Si-AMP. The proposed method was applied in the preconcentration and determination of Cu(II) in a fresh water sample from the Paraná river and was validated through a comparative analysis of a standard reference material (1643e).

Effects of organic solvents on immobilized lipase in pectin microspheres.

Lipase from Brevibacillus agri 52 was found stable up to 90% diethylenglycol (DEG), glycerol (GLY), and 1,2 propanediol (1,2 PRO) at 37 degrees C for 1 h and the stability was reduced only approximately 20% after 12 h incubation, but in 40% dimethylsulfoxide (DMSO), lipase activity was stable only for 1 h. Inhibition of the biocatalysts with dimethylformamide (DMF) was detected at 20% solvent concentration. In water immiscible systems, the stability of lipase in n-hexane, n-tetradecane and n-heptane resembles the water activity, but in the presence of isobutanol, 1-hexanol, and butylbutirate, the stability was significantly reduced. Lipase 52 precipitates in the presence of 50% acetone or ethanol/water mixtures, but enzymatic activity was partially recovered by adding 20% GLY, DEG, 1,2 PRO, or DMSO to the reaction mixture. Furthermore, by increasing DEG in 70% DMF/DEG mixtures, the lipase activity was protected. Encapsulation of lipase in pectin gels cross-linked with calcium ions brings three to four times more enzymatic activity in 70% water miscible organic solvents compared to aqueous systems.

Magnetic properties of ZnO nanoparticles.

We experimentally show that it is possible to induce room-temperature ferromagnetic-like behavior in ZnO nanoparticles without doping with magnetic impurities but simply inducing an alteration of their electronic configuration. Capping ZnO nanoparticles ( approximately 10 nm size) with different organic molecules produces an alteration of their electronic configuration that depends on the particular molecule, as evidenced by photoluminescence and X-ray absorption spectroscopies and altering their magnetic properties that varies from diamagnetic to ferromagnetic-like behavior.