Development and Evaluation of Praziquantel Solid Dispersions in Sodium Starch Glycolate

Purpose: To develop and characterize solid dispersions of praziquantel (PZQ) with sodium starch glycolate (SSG) for enhanced drug solubility.Methods: PZQ solid dispersion (SD) was prepared using co-precipitation method by solvent evaporation. The ratios of PZQ to SSG were 2:1, 1:1, 1:2, 1:3 (w/w). PZQ solubility was evaluated in purified water, and PZQ dissolution test was carried out in 0.1N HCl. Structural characterization of the dispersions was accomplished by x-ray diffraction (XRD) and infrared spe ctroscopy (FTIR) while the external morphology of the SDs, SSG and PZQ were studied by scanning electron microscopy (SEM). Mucoadhesion properties of the SD (1:3) and SSG, on mucin disks were examined using texture profile analysis.Results: The highest solubility was obtained with 1:3 solid dispersion, with PZQ solubility of 97.31 %, which is 3.65-fold greater than the solubility of pure PZQ and physical misture (PM, 1:3). XRD results indicate a reduction in PZQ crystallinity while infrared spectra showed that the functional groups of PZQ and SSG were preserved. SEM showed that the physical structure of PZQ was modified from crystalline to amorphous. The amount of PZQ in PM and SD (1:3) that dissolved in 60 min was 70 and 88 %, respectively, and these values increased to 76 and 96 %, respectively. The solid dispersion reduced the mucoadhesive property of the glycolate.Conclusion: Solid dispersion formulation using SSG is a good alternative approach for increasing the dissolution rate of PZQ.Keywords: Praziquantel, Drug bioavailability, Schistosomiasis, Solid dispersion, Co-precipitation, Sodium starch glycolat

The Local Bias Model in the Large Scale Halo Distribution

We explore the biasing in the clustering statistics of halos as compared to dark matter (DM) in simulations. We look at the second and third order statistics at large scales of the (intermediate) MICEL1536 simulation and also measure directly the local bias relation h = f({\delta}) between DM fluctuations, {\delta}, smoothed over a top-hat radius Rs at a point in the simulation and its corresponding tracer h (i.e. halos) at the same point. This local relation can be Taylor expanded to define a linear (b1) and non-linear (b2) bias parameters. The values of b1 and b2 in the simulation vary with Rs approaching a constant value around Rs > 30 - 60 Mpc/h. We use the local relation to predict the clustering of the tracer in terms of the one of DM. This prediction works very well (about percent level) for the halo 2-point correlation {\xi}(r_12) for r_12 > 15 Mpc/h, but only when we use the biasing values that we found at very large smoothing radius Rs > 30 - 60 Mpc/h. We find no effect from stochastic or next to leading order terms in the f({\delta}) expansion. But we do find some discrepancies in the 3-point function that needs further understanding. We also look at the clustering of the smoothed moments, the variance and skewness which are volume average correlations and therefore include clustering from smaller scales. In this case, we find that both next to leading order and discreetness corrections (to the local model) are needed at the 10 - 20% level. Shot-noise can be corrected with a term {\sigma}e^2/n where {\sigma}e^2 < 1, i.e., always smaller than the Poisson correction. We also compare these results with the peak-background split predictions from the measured halo mass function. We find 5-10% systematic (and similar statistical) errors in the mass estimation when we use the halo model biasing predictions to calibrate the mass.Comment: Accepted in MNRAS. Compared to first version, the paper has been completely reorganised. New figures and content adde

Pseudoboehmite as a drug delivery system for acyclovir

Herpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and it is indicated for the treatment and management of recurrent cold sores on the lips and face, genital herpes, among other diseases. The problem of the oral bioavailability of acyclovir is limited because of the low permeability across the gastrointestinal membrane. The use of nanoparticles of pseudoboehmite as a drug delivery system in vitro assays is a promising approach to further the permeability of acyclovir release. Here we report the synthesis of high purity pseudoboehmite from aluminium nitrate and ammonium hydroxide containing nanoparticles, using the sol–gel method, as a drug delivery system to improve the systemic bioavailability of acyclovir. The presence of pseudoboehmite nanoparticles were verified by infrared spectroscopy, transmission electron microscopy, and X-ray diffraction techniques. In vivo tests were performed with Wistar rats to compare the release of acyclovir, with and without the addition of pseudoboehmite. The administration of acyclovir with the addition of pseudoboehmite increased the drug content by 4.6 times in the plasma of Wistar rats after 4 h administration. We determined that the toxicity of pseudoboehmite is low up to 10 mg/mL, in gel and the dried pseudoboehmite nanoparticles.The authors thank the Mackenzie Presbyterian University, Texas Tech University, Mack Pesquisa, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES), Cnpq, and FAPESP (grant 2010/19157-9 and grant 2017/22396-4) for the sponsorship to this project

Fitting the incidence data from the city of Campinas, Brazil, based on dengue transmission modellings considering time-dependent entomological parameters

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFour time-dependent dengue transmission models are considered in order to fit the incidence data from the City of Campinas, Brazil, recorded from October 1st 1995 to September 30th 2012. The entomological parameters are allowed to depend on temperature and precipitation, while the carrying capacity and the hatching of eggs depend only on precipitation. The whole period of incidence of dengue is split into four periods, due to the fact that the model is formulated considering the circulation of only one serotype. Dengue transmission parameters from human to mosquito and mosquito to human are fitted for each one of the periods. The time varying partial and overall effective reproduction numbers are obtained to explain the incidence of dengue provided by the models.Four time-dependent dengue transmission models are considered in order to fit the incidence data from the City of Campinas, Brazil, recorded from October 1st 1995 to September 30th 2012. The entomological parameters are allowed to depend on temperature and precipitation, while the carrying capacity and the hatching of eggs depend only on precipitation. The whole period of incidence of dengue is split into four periods, due to the fact that the model is formulated considering the circulation of only one serotype. Dengue transmission parameters from human to mosquito and mosquito to human are fitted for each one of the periods. The time varying partial and overall effective reproduction numbers are obtained to explain the incidence of dengue provided by the models113FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2009/15098-

Two rapid assays for screening of patulin biodegradation

Artículo sobre distintos ensayos para comprobar la biodegradación de la patulinaThe mycotoxin patulin is produced by the blue mould pathogen Penicillium expansum in rotting apples during postharvest storage. Patulin is toxic to a wide range of organisms, including humans, animals, fungi and bacteria. Wash water from apple packing and processing houses often harbours patulin and fungal spores, which can contaminate the environment. Ubiquitous epiphytic yeasts, such as Rhodosporidium kratochvilovae strain LS11 which is a biocontrol agent of P. expansum in apples, have the capacity to resist the toxicity of patulin and to biodegrade it. Two non-toxic products are formed. One is desoxypatulinic acid. The aim of the work was to develop rapid, high-throughput bioassays for monitoring patulin degradation in multiple samples. Escherichia coli was highly sensitive to patulin, but insensitive to desoxypatulinic acid. This was utilized to develop a detection test for patulin, replacing time-consuming thin layer chromatography or high-performance liquid chromatography. Two assays for patulin degradation were developed, one in liquid medium and the other in semi-solid medium. Both assays allow the contemporary screening of a large number of samples. The liquid medium assay utilizes 96-well microtiter plates and was optimized for using a minimum of patulin. The semisolid medium assay has the added advantage of slowing down the biodegradation, which allows the study and isolation of transient degradation products. The two assays are complementary and have several areas of utilization, from screening a bank of microorganisms for biodegradation ability to the study of biodegradation pathways

Geometrical tests of cosmological models. III. The cosmology-evolution diagram at z=1

The rotational velocity of distant galaxies, when interpreted as a size (luminosity) indicator, may be used as a tool to select high redshift standard rods (candles) and probe world models and galaxy evolution via the classical angular diameter-redshift or Hubble diagram tests. We implement the proposed testing strategy using a sample of 30 rotators spanning the redshift range 0.2<z<1 with high resolution spectra and images obtained by the VIMOS/VLT Deep Redshift Survey (VVDS) and the Great Observatories Origins Deep Survey (GOODs). We show that by applying at the same time the angular diameter-redshift and Hubble diagrams to the same sample of objects (i.e. velocity selected galactic discs) one can derive a characteristic chart, the cosmology-evolution diagram, mapping the relation between global cosmological parameters and local structural parameters of discs such as size and luminosity. This chart allows to put constraints on cosmological parameters when general prior information about discs evolution is available. In particular, by assuming that equally rotating large discs cannot be less luminous at z=1 than at present (M(z=1) < M(0)), we find that a flat matter dominated cosmology (Omega_m=1) is excluded at a confidence level of 2sigma and an open cosmology with low mass density (Omega_m = 0.3) and no dark energy contribution is excluded at a confidence level greater than 1 sigma. Inversely, by assuming prior knowledge about the cosmological model, the cosmology-evolution diagram can be used to gain useful insights about the redshift evolution of the structural parameters of baryonic discs hosted in dark matter halos of nearly equal masses.Comment: 14 pages and 11 figures. A&A in pres

Probing the cosmic microwave background temperature using the Sunyaev-Zeldovich effect

We discuss the possibility to constrain the relation between redshift and temperature of the cosmic microwave background (CMB) using multifrequency Sunyaev-Zeldovich (SZ) observations. We have simulated a catalog of clusters of galaxies detected through their SZ signature assuming the sensitivities that will be achieved by the {\it Planck} satellite at 100, 143 and 353 GHz, taking into account the instrumental noise and the contamination from the Cosmic Infrared Background and from unresolved radiosources. We have parametrized the cosmological temperature-redshift law as $T\propto (1+z)^{(1-a)}$. Using two sets of SZ flux density ratios (100/143 GHz, which is most sensitive to the parametrization of the $T-z$ law, and 143/353 GHz, which is most sensitive to the peculiar velocities of the clusters) we show that it is possible to recover the $T-z$ law assuming that the temperatures and redshifts of the clusters are known. From a simulated catalog of $\sim 1200$ clusters, the parameter $a$ can be recovered to an accuracy of 10$^{-2}$. Sensitive SZ observations thus appear as a potentially useful tool to test the standard law. Most cosmological models predict a linear variation of the CMB temperature with redshift. The discovery of an alternative law would have profound implications on the cosmological model, implying creation of energy in a manner that would still maintain the black-body shape of the CMB spectrum at redshift zero.Comment: 8 pages, 9 figures, submitted to A&