Tyrosine-based rivastigmine-loaded organogels in the treatmant of Alzheimer's disease

Faculté de PharmacieOrganogels can be prepared by immobilizing an organic phase into a threedimensional network coming from the self-assembly of a low molecular weight gelator molecule. In this work, an injectable subcutaneous organogel system based on safflower oil and a modified-tyrosine organogelator was evaluated in vivo for the delivery of rivastigmine, an acetylcholinesterase (AChE) inhibitor used in the treatment of Alzheimer’s disease. Different implant formulations were injected and the plasmatic drug concentration was assayed for up to 35 days. In parallel, the inhibition of AChE in different brain sections and the biocompatibility of the implants were monitored. The pharmacokinetic profiles were found to be influenced by the gel composition, injected dose and volume of the implant. The sustained delivery of rivastigmine was accompanied by a significant prolonged inhibition of AChE in the hippocampus, a brain structure involved in memory. The implant induced only a minimal to mild chronic inflammation and fibrosis, which was comparable to poly(D,L-lactide-co-glycolide) in situ-forming implants. These findings suggest that tyrosine-based organogels could represent an alternative approach to current formulations for the sustained delivery of cholinesterase inhibitors.IRS

Nanonization of megestrol acetate by laser fragmentation in aqueous milieu

Faculté de PharmacieNanonization is a simple and effective method to improve dissolution rate and oral bioavailability of drugs with poor water solubility. There is growing interest to downscale the nanocrystal production to enable early preclinical evaluation of new drug candidates when compound availability is scarce. The purpose of the present study was to investigate laser fragmentation to form nanosuspensions in aqueous solution of the insoluble model drug megestrol acetate (MA) using very little quantities of the drug. Laser fragmentation was obtained by focusing a femtosecond (fs) or nanosecond (ns) laser radiation on a magnetically stirred MA suspension in water or aqueous solution of a stabilizing agent. The size distribution and physicochemical properties of the drug nanoparticles were characterized, and the in vitro dissolution and in vivo oral pharmacokinetics of a laser fragmented formulation were evaluated. A MA nanosuspension was also prepared by media milling for comparison purpose. For both laser radiations, smaller particles were obtained as the laser power was increased, but at a cost of higher degradation. Significant nanonization was achieved after a 30-min fs laser treatment at 250 mW and a 1-h ns laser treatment at 2500 mW. The degradation induced by the laser process of the drug was primarily oxidative in nature. The crystal phase of the drug was maintained, although partial loss of crystallinity was observed. The in vitro dissolution rate and in vivo bioavailability of the laser fragmented formulation were similar to those obtained with the nanosuspension prepared by media milling, and significantly improved compared to the coarse drug powder. It follows that this laser nanonization method has potential to be used for the preclinical evaluation of new drug candidates.IRSC - CRNS

Les interstices en institution

Mediante numerosos ejemplos y experiencias personales sobre la dinámica grupal, se establece un diálogo cercano a los lectores, para aportar elementos que permitan comprender los espacios y procesos intersticiales que se presentan de manera necesaria en las instituciones, en particular, las de salud mental. Se describen tres tipos de amenaza a los intersticios: la relacionada con el management, con aspectos procedimentales, y con la fetichización del marco. En las instituciones, los intersticios se presentan como espacio-tiempos de elaboración, o como procesos. A continuación, se caracterizan tres formas de grupalidad que se pueden presentar en las instituciones en: G1, G2, G3; así como los intersticios y temporalidades que se pueden dar en ellas. Se cierra con un análisis de la relación con adolescentes, especialmente en el espacio de los Centros de Atención de Día a Jóvenes. Se plantea que en muchos sentidos los jóvenes se encuentran en migración y por tanto, en una condición propicia para los procesos intersticiales que los transforman

Los intersticios en la institución Jean Furtos

Mediante numerosos ejemplos y experiencias personales sobre la dinámica grupal, se establece un diálogo cercano a los lectores, para aportar elementos que permitan comprender los espacios y procesos intersticiales que se presentan de manera necesaria en las instituciones, en particular, las de salud mental. Se describen tres tipos de amenaza a los intersticios: la relacionada con el management, con aspectos procedimentales, y con la fetichización del marco. En las instituciones, los intersticios se presentan como espacio-tiempos de elaboración, o como procesos. A continuación, se caracterizan tres formas de grupalidad que se pueden presentar en las instituciones en: G1, G2, G3; así como los intersticios y temporalidades que se pueden dar en ellas. Se cierra con un análisis de la relación con adolescentes, especialmente en el espacio de los Centros Día de Atención a Jóvenes. Se plantea que en muchos sentidos los jóvenes se encuentran en migración y por tanto, en una condición propicia para los procesos intersticiales que los transforman

Chemical and Structural Assessment of New Dental Composites with Graphene Exposed to Staining Agents

Among the newest trends in dental composites is the use of graphene oxide (GO) nanoparticles to assure better cohesion of the composite and superior properties. Our research used GO to enhance several hydroxyapatite (HA) nanofiller distribution and cohesion in three experimental composites CC, GS, GZ exposed to coffee and red wine staining environments. The presence of silane A-174 on the filler surface was evidenced by FT-IR spectroscopy. Experimental composites were characterized through color stability after 30 days of staining in red wine and coffee, sorption and solubility in distilled water and artificial saliva. Surface properties were measured by optical profilometry and scanning electron microscopy, respectively, and antibacterial properties wer e assessed against Staphylococcus aureus and Escherichia coli. A colour stability test revealed the best results for GS, followed by GZ, with less stability for CC. Topographical and morphological aspects revealed a synergism between GZ sample nanofiller components that conducted to the lower surface roughness, with less in the GS sample. However, surface roughness variation due to the stain was affected less than colour stability at the macroscopic level. Antibacterial testing revealed good effect against Staphylococcus aureus and a moderate effect against Escherichia coli

RADIOPACITY ANALYSIS OF SOME CHAIRSIDE COMPUTER-AIDED DESIGN-COMPUTER-AIDED MANUFACTURING MILLING MATERIALS

In this study, the radiopacity of chairside Computer-Aided Design-Computer-Aided Manufacturing (CAD-CAM) milling materials was evaluated in comparison with dental structures. 105 specimens of 7 different thicknesses from 5 different types of chairside CAD-CAM milling materials: feldspar ceramic, hybrid ceramic, lithium disilicate glass-ceramic, zirconia-reinforced lithium silicate ceramic and a resin nano-ceramic were used for this in vitro study. Digital radiographs were obtained using an aluminum step wedge, a specimen of a tooth slice and 3 specimens from each material. Radiodensity was determined for each material using dedicated software. Lava Ultimate and Vita Suprinity were found as having higher radiopacity, whilst Vita Mark II and Vita Enamic were lower in radiopacity in comparison with dental structures. The radiodensity of Emax CAD was between enamel and dentine. Radiopacity of each CAD-CAM milling material was different and both material’s type and thickness significantly affected the radiopacity

Novel bioresorbable phosphate glass fiber textile composites for medical applications

A manual bench-top inkle-type loom was designed to enable hand woven textiles. These PGF textiles, along with unidirectional (UD) fiber mats made from the same batch of yarns, were utilized to manufacture fully resorbable textile composites (T-C), unidirectional aligned fiber composites (UD-C) and 0°/90° lay-up UD fiber reinforced composites (0/90-C). The fiber volume fraction in the composites was set at ~20%. Retention of flexural properties and mass loss of the composites were evaluated during degradation in phosphate buffered saline (PBS) at 37 °C for 28 days. The higher flexural strength and modulus values observed for the T-C when compared to 0/90-C were attributed to the textile weaving resulting in a biased fabric with a higher density of fibers in the warp direction. After 28 days immersion in PBS ~20% flexural strength and ~25% flexural modulus values for the UD-C, T-C and 0/90-C composites were still prevalent