Solid Dispersion of Ursolic Acid in Gelucire 50/13: a Strategy to Enhance Drug Release and Trypanocidal Activity

Solid dispersions (SDs) are an approach to increasing the water solubility and bioavailability of lipophilic drugs such as ursolic acid (UA), a triterpenoid with trypanocidal activity. In this work, Gelucire 50/13, a surfactant compound with permeability-enhancing properties, and silicon dioxide, a drying adjuvant, were employed to produce SDs with UA. SDs and physical mixtures (PMs) in different drug/carrier ratios were characterized and compared using differential scanning calorimetry, hot stage microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), particle size, water solubility values, and dissolution profiles. Moreover, LLC-MK2 fibroblast cytotoxicity and trypanocidal activity evaluation were performed to determine the potential of SD as a strategy to improve UA efficacy against Chagas disease. The results demonstrated the conversion of UA from the crystalline to the amorphous state through XRD. FTIR experiments provided evidence of intermolecular interactions among the drug and carriers through carbonyl peak broadening in the SDs. These findings helped explain the enhancement of water solubility from 75.98 mu g/mL in PMs to 293.43 mu g/mL in SDs and the faster drug release into aqueous media compared with pure UA or PMs, which was maintained after 6 months at room temperature. Importantly, improved SD dissolution was accompanied by higher UA activity against trypomastigote forms of Trypanosoma cruzi, but not against mammalian fibroblasts, enhancing the potential of UA for Chagas disease treatment.

Understanding the solid forms of 5E-phenylethenylbenzofuroxan with different in vivo anti-T. cruzi activity

5E-Phenylethenylbenzofuroxan (5PhEBfx) was reported as an excellent anti-Chagas drug candidate. However, its oral bioavailability was affected by the crystallization process. Two samples exhibiting variable in vivo activity was investigated: a thin yellow powder (5PhEBfx-Y) and orange needles (5PhEBfx-O). X-ray powder diffraction, differential scanning calorimetry, vibrational spectroscopy, optical and electron scanning microscopies were applied to investigate both solid forms in order to correlate the solid-state properties with the variable bioavailability of 5PhEBfx. It was observed that 5PhEBfx-Y have a better solubility and consequently higher bioavailability when compared with 5PhEBfx-O. This result suggests that the difference of activity between these two 5E-Phenylethenylbenzofuroxanes could be associated with the solid forms, which also cause the coloration variation.

Conformational polymorphism of the antidiabetic drug chlorpropamide

In this paper, the main features of Raman spectroscopy, one of the first choice methods in the study of polymorphism in pharmaceuticals, are presented taking chlorpropamide as a case of study. The antidiabetic drug chlorpropamide (1-[4-chlorobenzenesulphonyl]-3-propyl urea), which belongs to the sulfonylurea class, is known to exhibit, at least, six polymorphic phases. These forms are characterized not only by variations in their molecular packing but also in their molecular conformation. In this study, the polymorphism of chlorpropamide is discussed on the basis of Raman scattering measurements and quantum mechanical calculations. The main spectroscopic features that fingerprint the crystalline forms are correlated with the corresponding crystalline structures. Using a theoretical approach on the energy dependence of the conformers, simulated molecular torsion angles are plotted versus the formation energy, which provides a satisfactory agreement between the torsion angles at the energy minima and the experimental values observed in the different solid forms of chlorpropamide. Copyright (C) 2011 John Wiley & Sons, Ltd.

Prey digestion in the midgut of the predatory bug Podisus nigrispinus (Hemiptera: Pentatomidae)

Pre-oral digestion is described as the liquefaction of the solid tissues of the prey by secretions of the predator. It is uncertain if pre-oral digestion means pre-oral dispersion of food or true digestion in the sense of the stepwise bond breaking of food polymers to release monomers to be absorbed. Collagenase is the only salivary proteinase, which activity is significant (10%) in relation to Podisus nigrispinus midgut activities. This suggests that pre-oral digestion in P. nigrispinus consists in prey tissue dispersion. This was confirmed by the finding of prey muscles fibers inside P. nigrispinus midguts. Soluble midgut hydrolases from P. nigrispinus were partially purified by ion-exchange chromatography, followed by gel filtration. Two cathepsin L-like proteinases (CAL1 and CAL2) were isolated with the properties: CAL1 (14.7 kDa, pH optimum (pHo) 5.5, km with carbobenzoxy-Phe-Arg-methylcoumarin, Z-FR-MCA, 32 mu M); CAL2 (17 kDa, pHo 5.5, km 11 mu M Z-FR-MCA). Only a single molecular species was found for the other enzymes with the following properties are: amylase (43 kDa, pHo 5.5, km 0.1% starch), aminopeptidase (125 kDa, pHo 5.5, km 0.11 mM L-Leucine-p-nitroanilide), alpha-glucosidase (90 kDa, pHo 5.0, km 5 mM with p-nitrophenyl alpha-D-glucoside). CAL molecular masses are probably underestimated due to interaction with the column. Taking into account the distribution of hydrolases along P. nigrispinus midguts, carbohydrate digestion takes place mainly at the anterior midgut, whereas protein digestion occurs mostly in middle and posterior midgut, as previously described in seed- sucker and blood-feeder hemipterans. (C) 2012 Elsevier Ltd. All rights reserved.

Minimally invasive esthetic therapy: a case report describing the advantages of a multidisciplinary approach

The decision-making process for the treatment of esthetic areas is based on the achievement of a healthy, harmonious, and pleasant smile. These conditions are directly associated with a solid knowledge of tooth anatomy and proportions, as well as the smile line, soft tissue morphology, and osseous architecture. To achieve these objectives, a multidisciplinary approach may be necessary to create long-term harmony between the final restoration and the adjacent teeth, and the health of the surrounding soft and hard tissues. This case report describes the application of a minimally invasive therapy on a 33-year-old woman seeking esthetic treatment. Minimally invasive periodontal plastic surgery associated with porcelain laminate veneers yielded satisfactory esthetics and minimal trauma to dental and periodontal tissues. Such a combined approach may be considered a viable option for the improvement of "white" and "red" esthetics.

Boron site preference in ternary Ta and Nb boron suicides

X-ray single crystal (XSC) and neutron powder diffraction data (NPD) were used to elucidate boron site preference for five ternary phases. Ta3Si1-xBx (x=0.112(4)) crystallizes with the Ti3P-type (space group P4(2)/n) with B-atoms sharing the 8g site with Si atoms. Ta5Si3-x (x=0.03(1); Cr5B3- type) crystallizes with space group 14/mcm, exhibiting a small amount of vacancies on the 4 alpha site. Both, Ta-5(Si1-xBx)(3), X=0.568(3), and Nb-5(Si1-xBx)(3), x=0.59(2), are part of solid solutions of M5Si3 with Cr5B3-type into the ternary M-Si-B systems (M=Nb or Ta) with B replacing Si on the 8h site. The D8(8)-phase in the Nb-Si-B system crystallizes with the Ti5Ga4-type revealing the formula Nb5Si3B1-x (x=0.292(3)) with B partially filling the voids in the 2b site of the Mn5Si3 parent type. (C) 2012 Elsevier Inc. All rights reserved.

Surface Segregation in Chromium-Doped Nanocrystalline Tin Dioxide Pigments

Surface properties play an important role in understanding and controlling nanocrystalline materials. The accumulation of dopants on the surface, caused by surface segregation, can therefore significantly affect nanomaterials properties at low doping levels, offering a way to intentionally control nanoparticles features. In this work, we studied the distribution of chromium ions in SnO2 nanoparticles prepared by a liquid precursor route at moderate temperatures (500 degrees C). The powders were characterized by infrared spectroscopy, X-ray diffraction, (scanning) transmission electron microscopy, Electron Energy Loss Spectroscopy, and Mossbauer spectroscopy. We showed that this synthesis method induces a limited solid solution of chromium into SnO2 and a segregation of chromium to the surface. The s-electron density and symmetry of Sn located on the surface were significantly affected by the doping, while Sn located in the bulk remained unchanged. Chromium ions located on the surface and in the bulk showed distinct oxidation states, giving rise to the intense violet color of the nanoparticles suitable for pigment application.

Statistical models for experimental model membranes.

Biological membranes are constituted from lipid bilayers and proteins. Investigation of protein-membrane interaction, essential for biological function of cells, must rest upon solid knowledge of lipid bilayer behavior. Thus, extensive studies of an experimental model for membranes, lipid bilayers in water solution, have been undertaken in the last decades. These systems present structural, thermal and electrical properties which depend on temperature, ionic strength or concentration. In this talk, we shall discuss statistical models for lipid bilayers, as well as the relation between their properties and results for properties of lipid dispersions investigated by the laboratories supervised by Teresa Lamy (IF-USP) and Amando Ito (FFCL-USP).