87 research outputs found
Lipid nanoparticles for cyclosporine a administration: Development, characterization, and in vitro evaluation of their immunosuppression activity
Cyclosporine A (CsA) is an immunosuppressant commonly used in transplantation for prevention of organ rejection as well as in the treatment of several autoimmune disorders. Although commercial formulations are available, they have some stability, bioavailability, and toxicity related problems. Some of these issues are associated with the drug or excipients and others with the dosage forms. With the aim of overcoming these drawbacks, lipid nanoparticles (LN) have been proposed as an alternative, since excipients are biocompatible and also a large amount of surfactants and organic solvents can be avoided. CsA was successfully incorporated into LN using the method of hot homogenization followed by ultrasonication. Three different formulations were optimized for CsA oral administration, using different surfactants: Tween® 80, phosphatidylcholine, taurocholate and Pluronic® F127 (either alone or mixtures). Freshly prepared Precirol nanoparticles showed mean sizes with a narrow size distribution ranging from 121 to 202 nm, and after freeze-drying were between 163 and 270 nm, depending on the stabilizer used. Surface charge was negative in all LN developed. High CsA entrapment efficiency of approximately 100% was achieved. Transmission electron microscopy was used to study the morphology of the optimized LN. Also, the crystallinity of the nanoparticles was studied by X-ray powder diffraction and differential scanning calorimetry. The presence of the drug in LN surfaces was confirmed by X-ray photoelectron spectroscopy. The CsA LN developed preserved their physicochemical properties for 3 months when stored at 4°C. Moreover, when the stabilizer system was composed of two surfactants, the LN formulations were also stable at room temperature. Finally, the new CsA formulations showed in vitro dose-dependent immunosuppressive effects caused by the inhibition of IL-2 levels secreted from stimulated Jurkat cells. The findings obtained in this paper suggest that new lipid nanosystems are a good alternative to produce physicochemically stable CsA formulations for oral administration
LAGOVirtual: A Collaborative Environment for the Large Aperture GRB Observatory
We present the LAGOVirtual Project: an ongoing project to develop platform to
collaborate in the Large Aperture GRB Observatory (LAGO). This continental-wide
observatory is devised to detect high energy (around 100 GeV) component of
Gamma Ray Bursts, by using the single particle technique in arrays of Water
Cherenkov Detectors (WCD) at high mountain sites (Chacaltaya, Bolivia, 5300 m
a.s.l., Pico Espejo, Venezuela, 4750 m a.s.l., Sierra Negra, Mexico, 4650 m
a.s.l). This platform will allow LAGO collaboration to share data, and computer
resources through its different sites. This environment has the possibility to
generate synthetic data by simulating the showers through AIRES application and
to store/preserve distributed data files collected by the WCD at the LAGO
sites. The present article concerns the implementation of a prototype of
LAGO-DR adapting DSpace, with a hierarchical structure (i.e. country,
institution, followed by collections that contain the metadata and data files),
for the captured/simulated data. This structure was generated by using the
community, sub-community, collection, item model; available at the DSpace
software. Each member institution-country of the project has the appropriate
permissions on the system to publish information (descriptive metadata and
associated data files). The platform can also associate multiple files to each
item of data (data from the instruments, graphics, postprocessed-data, etc.).Comment: Second EELA-2 Conference Choroni, Venezuela, November 25th to 27th
200
Photoluminescence Imaging and LBIC Characterization of Defects in mc-Si Solar Cells
Today's photovoltaic market is dominated by multicrystalline silicon (mc-Si) based solar cells with around 70% of worldwide production. In order to improve the quality of the Si material, a proper characterization of the electrical activity in mc-Si solar cells is essential. A full-wafer characterization technique such as photoluminescence imaging (PLi) provides a fast inspection of the wafer defects, though at the expense of the spatial resolution. On the other hand, a study of the defects at a microscopic scale can be achieved through the light-beam induced current technique. The combination of these macroscopic and microscopic resolution techniques allows a detailed study of the electrical activity of defects in mc-Si solar cells. In this work, upgraded metallurgical-grade Si solar cells are studied using these two techniques
Ultra high performance liquid chromatography–tandem mass spectrometry method for cyclosporine a quantification in biological samples and lipid nanosystems
Cyclosporine A (CyA) is an immunosuppressant cyclic undecapeptide used for the prevention of organ transplant rejection and in the treatment of several autoimmune disorders. An ultra high performance liquid chromatography–tandem mass spectrometry method (UHPLC–MS/MS) to quantify CyA in lipid nanosystems and mouse biological matrices (whole blood, kidneys, lungs, spleen, liver, heart, brain, stomach and intestine) was developed and fully validated. Chromatographic separation was performed on an Acquity UPLC® BEH C18 column with a gradient elution consisting of methanol and 2 mM ammonium acetate aqueous solution containing 0.1% formic acid at a flow rate of 0.6 mL/min. Amiodarone was used as internal standard (IS). Retention times of IS and CyA were 0.69 min and 1.09 min, respectively. Mass spectrometer operated in electrospray ionization positive mode (ESI+) and multiple reaction monitoring (MRM) transitions were detected, m/z 1220.69 → 1203.7 for CyA and m/z 646 → 58 for IS. The extraction method from biological samples consisted of a simple protein precipitation with 10% trichloroacetic acid aqueous solution and acetonitrile and 5 μL of supernatant were directly injected into the UHPLC–MS/MS system. Linearity was observed between 0.001 μg/mL–2.5 μg/mL (r ≥ 0.99) in all matrices. The precision expressed in coefficient of variation (CV) was below 11.44% and accuracy in bias ranged from −12.78% to 7.99% including methanol and biological matrices. Recovery in all cases was above 70.54% and some matrix effect was observed. CyA was found to be stable in post-extraction whole blood and liver homogenate samples exposed for 6 h at room temperature and 72 h at 4 °C. The present method was successfully applied for quality control of lipid nanocarriers as well as in vivo studies in BALB/c mice
The Large Aperture GRB Observatory
The Large Aperture GRB Observatory (LAGO) is aiming at the detection of the
high energy (around 100 GeV) component of Gamma Ray Bursts, using the single
particle technique in arrays of Water Cherenkov Detectors (WCD) in high
mountain sites (Chacaltaya, Bolivia, 5300 m a.s.l., Pico Espejo, Venezuela,
4750 m a.s.l., Sierra Negra, Mexico, 4650 m a.s.l). WCD at high altitude offer
a unique possibility of detecting low gamma fluxes in the 10 GeV - 1 TeV range.
The status of the Observatory and data collected from 2007 to date will be
presented.Comment: 4 pages, proceeding of 31st ICRC 200
Water Cherenkov Detectors response to a Gamma Ray Burst in the Large Aperture GRB Observatory
In order to characterise the behaviour of Water Cherenkov Detectors (WCD)
under a sudden increase of 1 GeV - 1 TeV background photons from a Gamma Ray
Burst (GRB), simulations were conducted and compared to data acquired by the
WCD of the Large Aperture GRB Observatory (LAGO). The LAGO operates arrays of
WCD at high altitude to detect GRBs using the single particle technique. The
LAGO sensitivity to GRBs is derived from the reported simulations of the gamma
initiated particle showers in the atmosphere and the WCD response to
secondaries.Comment: 5 pages, proceeding of the 31st ICRC 200
In vitro intestinal co-culture cell model to evaluate intestinal absorption of edelfosine lipid nanoparticles
Nanotechnology is providing a new therapeutic paradigm by enhancing drug efficacy and preventing side-effects. Edelfosine is a synthetic ether lipid analogue of platelet activating factor with high antitumor activity. The encapsulation of this potent antitumor drug in lipid nanoparticles increases its oral bioavailability; moreover, it prevents the hemolytic and gastrointestinal side-effects of the free drug. The literature points towards lymphatic absorption of lipid nanoparticles after oral administration, and previous in vitro and in vivo studies stress the protection against toxicity that these nanosystems provide. The present study is intended to assess the permeability of lipid nanoparticles across the intestinal barrier. Caco-2 monoculture and Caco-2/Raji co-culture were used as in vitro models of enterocytes and Microfold cells respectively. Results showed that free drug is internalized and possibly metabolized in enterocytes. These results do not correlate with those observed in vivo when edelfosine-lipid nanoparticles were administered orally in mice, which suggests that the microfold model is not a good model to study the absorption of edelfosine-lipid nanoparticles across the intestinal barrier in vitro
Lipid nanoparticles for cyclosporine A administration: development, characterization, and in vitro evaluation of their immunosuppression activity
Cyclosporine A (CsA) is an immunosuppressant commonly used in transplantation for prevention of organ rejection as well as in the treatment of several autoimmune disorders. Although commercial formulations are available, they have some stability, bioavailability, and toxicity related problems. Some of these issues are associated with the drug or excipients and others with the dosage forms. With the aim of overcoming these drawbacks, lipid nanoparticles (LN) have been proposed as an alternative, since excipients are biocompatible and also a large amount of surfactants and organic solvents can be avoided. CsA was successfully incorporated into LN using the method of hot homogenization followed by ultrasonication. Three different formulations were optimized for CsA oral administration, using different surfactants: Tween® 80, phosphatidylcholine, taurocholate and Pluronic® F127 (either alone or mixtures). Freshly prepared Precirol nanoparticles showed mean sizes with a narrow size distribution ranging from 121 to 202 nm, and after freeze-drying were between 163 and 270 nm, depending on the stabilizer used. Surface charge was negative in all LN developed. High CsA entrapment efficiency of approximately 100% was achieved. Transmission electron microscopy was used to study the morphology of the optimized LN. Also, the crystallinity of the nanoparticles was studied by X-ray powder diffraction and differential scanning calorimetry. The presence of the drug in LN surfaces was confirmed by X-ray photoelectron spectroscopy. The CsA LN developed preserved their physicochemical properties for 3 months when stored at 4°C. Moreover, when the stabilizer system was composed of two surfactants, the LN formulations were also stable at room temperature. Finally, the new CsA formulations showed in vitro dose-dependent immunosuppressive effects caused by the inhibition of IL-2 levels secreted from stimulated Jurkat cells. The findings obtained in this paper suggest that new lipid nanosystems are a good alternative to produce physicochemically stable CsA formulations for oral administration
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