To overcome these challenges, we developed an enzyme-responsive, Panobinostat nanoparticle-in-microgel delivery system. This system is designed to provide optimal aerodynamic carrier size for deep lung delivery, improved residence time of carriers in the lungs
by avoiding rapid clearance by macrophages, and reduction of side effects and toxicity by releasing encapsulated therapeutics in response to disease-specific stimuli. This unique carrier system is fabricated using a new Michael addition during (water-in-oil) emulsion (MADE) method, especially suitable for biologic drugs due to its gentle fabrication conditions. The resulting microgels have a highly porous internal structure and an optimal aerodynamic diameter for effective deep lung delivery. They also exhibit SB-715992 in vivo triggered release of various nanoparticles and biologics in the presence of physiological levels of enzyme. In addition, the nanoparticle-carrying microgels showed little uptake by macrophages, indicating potential for increased lung residence time and minimal clearance by alveolar macrophages. Collectively, this system introduces a rationally designed, disease-specific, multi-tiered delivery system for use as an improved pulmonary carrier for biologic drugs. (C) 2012 Elsevier B. V. All rights reserved.”
“Siboglinid worms
live on carbohydrates produced by symbiotic bacteria. In this study, alpha-glucosidaselike activity Sapitinib concentration was detected in the surface of the body and in
the trophosome of Oligobrachia mashikoi. The enzyme exhibiting this activity was partially purified by consecutively applying the crude enzyme extract to Con-A-Sepharose and Sephadex-200 HR columns. The enzyme sample thus obtained gave a single activity peak at a position corresponding to 550 kDa in the Sephadex-200 HR gel filtration column. The enzyme was active in the range of pH 6.0-8.0, with a maximum activity at around pH 6.5. It specifically hydrolyzed maltose, and was inhibited by voglibose and miglitol. Moreover, a glucose transporter 2-like protein was detected by immunolhistochemical and Western-blotting analyses using anti-rat GLUT2 polyclonal antibody. These results raise the question how this unique species lives.”
“Background/Aims: The aim of this study was to map metabolic compensation and depression in Alzheimer’s disease (AD) on a voxel-by-voxel basis. Methods: Twenty-one heal thy elderly subjects and 25 AD patients underwent cerebral MR and FDG-PET imaging. All images were processed with SPM2, and whole-brain gray matter (GM) atrophy and hypometabolism maps were computed. Metabolic compensation and depression were assessed using Biological Parametric Mapping software. Results: GM atrophy and hypometabolism mapped to similar regions, with varying degrees of severity.