A study of some fundamental physicochemical variables on the morphology of mesoporous silica nanoparticles MCM-41 type

[EN] All variables affecting the morphology of mesoporous silica nanoparticles (MSN) should be carefully analyzed in order to truly tailored design their mesoporous structure according to their final use. Although complete control on MCM-41 synthesis has been already claimed, reproducibility and repeatability of results remain a big issue due to the lack of information reported in literature. Stirring rate, reaction volume, and system configuration (i.e., opened or closed reactor) are three variables that are usually omitted, making the comparison of product characteristics difficult. Specifically, the rate of solvent evaporation is seldom disclosed, and its influence has not been previously analyzed. These variables were systematically studied in this work, and they were proven to have a fundamental impact on final particle morphology. Hence, a high degree of circularity (C = 0.97) and monodispersed particle size distributions were only achieved when a stirring speed of 500 rpm and a reaction scale of 500 mL were used in a partially opened system, for a 2 h reaction at 80 degrees C. Well-shaped spherical mesoporous silica nanoparticles with a diameter of 95 nm, a pore size of 2.8 nm, and a total surface area of 954 m(2) g(-1) were obtained. Final characteristics made this product suitable to be used in biomedicine and nanopharmaceutics, especially for the design of drug delivery systems.This study was funded partially by Departamento Administrativo de Ciencia Tecnología e Innovación–COLCIENCIAS (recipient, Angela A. Beltrán-Osuna); Ministerio de Economía y Competitividad, MINECO, research number MAT2016-76039-C4-1-R (Recipient, José L. Gómez-Ribelles); and Universidad Nacional de Colombia, grant number DIB201010021438 (Recipient, Jairo E. Perilla).Beltrán-Osuna, A.; Gómez Ribelles, JL.; Perilla-Perilla, JE. (2017). 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Rivastigmine Lowers Aβ and Increases sAPPα Levels, Which Parallel Elevated Synaptic Markers and Metabolic Activity in Degenerating Primary Rat Neurons

Overproduction of amyloid-β (Aβ) protein in the brain has been hypothesized as the primary toxic insult that, via numerous mechanisms, produces cognitive deficits in Alzheimer's disease (AD). Cholinesterase inhibition is a primary strategy for treatment of AD, and specific compounds of this class have previously been demonstrated to influence Aβ precursor protein (APP) processing and Aβ production. However, little information is available on the effects of rivastigmine, a dual acetylcholinesterase and butyrylcholinesterase inhibitor, on APP processing. As this drug is currently used to treat AD, characterization of its various activities is important to optimize its clinical utility. We have previously shown that rivastigmine can preserve or enhance neuronal and synaptic terminal markers in degenerating primary embryonic cerebrocortical cultures. Given previous reports on the effects of APP and Aβ on synapses, regulation of APP processing represents a plausible mechanism for the synaptic effects of rivastigmine. To test this hypothesis, we treated degenerating primary cultures with rivastigmine and measured secreted APP (sAPP) and Aβ. Rivastigmine treatment increased metabolic activity in these cultured cells, and elevated APP secretion. Analysis of the two major forms of APP secreted by these cultures, attributed to neurons or glia based on molecular weight showed that rivastigmine treatment significantly increased neuronal relative to glial secreted APP. Furthermore, rivastigmine treatment increased α-secretase cleaved sAPPα and decreased Aβ secretion, suggesting a therapeutic mechanism wherein rivastigmine alters the relative activities of the secretase pathways. Assessment of sAPP levels in rodent CSF following once daily rivastigmine administration for 21 days confirmed that elevated levels of APP in cell culture translated in vivo. Taken together, rivastigmine treatment enhances neuronal sAPP and shifts APP processing toward the α-secretase pathway in degenerating neuronal cultures, which mirrors the trend of synaptic proteins, and metabolic activity

PPARα Deficiency in Inflammatory Cells Suppresses Tumor Growth

Inflammation in the tumor bed can either promote or inhibit tumor growth. Peroxisome proliferator-activated receptor (PPAR)α is a central transcriptional suppressor of inflammation, and may therefore modulate tumor growth. Here we show that PPARα deficiency in the host leads to overt inflammation that suppresses angiogenesis via excess production of the endogenous angiogenesis inhibitor thrombospondin-1 and prevents tumor growth. Bone marrow transplantation and granulocyte depletion show that PPARα expressing granulocytes are necessary for tumor growth. Neutralization of thrombospondin-1 restores tumor growth in PPARα-deficient mice. These findings suggest that the absence of PPARα activity renders inflammatory infiltrates tumor suppressive and, thus, may provide a target for inhibiting tumor growth by modulating stromal processes, such as angiogenesis

ACTIVE TARGETING WITH PARTICULATE CARRIER SYSTEMS IN THE BLOOD COMPARTMENT

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Targeted liposomes for delivery of protein-based drugs into the cytoplasm of tumor cells

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