Versatile preparation of silica nanocapsules for biomedical applications

Core–shell nanocapsules are receiving increasing interest for drug delivery applications. Silica nanocapsules have been the focus of intensive studies due to their biocompatibility, versatile silica chemistry, and tunable porosity. However, a versatile one-step preparation of silica nanocapsules with well-defined core–shell structure, tunable size, flexible interior loading, and tailored shell composition, permeability, and surface functionalization for site-specific drug release and therapeutic tracking remains a challenge. Herein, an interfacially confined sol–gel process in miniemulsion for the one-step versatile preparation of functional silica nanocapsules is developed. Uniform nanocapsules with diameters from 60 to 400 nm are obtained and a large variety of hydrophobic liquids are encapsulated in the core. When solvents with low boiling point are loaded, subsequent solvent evaporation converts the initially hydrophobic cavity into an aqueous environment. Stimuli-responsive permeability of nanocapsules is programmed by introducing disulfide or tetrasulfide bonds in the shell. Selective and sustained release of dexamethasone in response to glutathione tripeptide for over 10 d is achieved. Fluorescence labeling of the silica shell and magnetic loading in the internal cavity enable therapeutic tracking of nanocapsules by fluorescence and electron microscopies. Thus, silica nanocapsules represent a promising theranostic nanoplatform for targeted drug delivery applications.Fil: Jiang, Shuai. Max Planck Institute for Polymer Research; AlemaniaFil: Mottola, Milagro. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Max Planck Institute For Polymer Research; AlemaniaFil: Han, Shen. Max Planck Institute For Polymer Research; AlemaniaFil: Thiramanas, Raweewan. Max Planck Institute For Polymer Research; AlemaniaFil: Graf, Robert. Max Planck Institute For Polymer Research; AlemaniaFil: Lieberwirth, Ingo. Max Planck Institute For Polymer Research; AlemaniaFil: Mailänder, Volker. Max Planck Institute For Polymer Research; AlemaniaFil: Crespy, Daniel. Max Planck Institute For Polymer Research; AlemaniaFil: Landfester, Katharina. Max Planck Institute For Polymer Research; Alemani

Controlling protein interactions in blood for effective liver immunosuppressive therapy by silica nanocapsules

Immunosuppression with glucocorticoids is a common treatment for autoimmune liver diseases and after liver transplant, which is however associated with severe side-effects. Targeted delivery of glucocorticoids to inflammatory cells, e.g. liver macrophages and Kupffer cells, is a promising approach for minimizing side effects. Herein, we prepare core–shell silica nanocapsules (SiO2 NCs) via a sol–gel process confined in nanodroplets for targeted delivery of dexamethasone (DXM) for liver immunosuppressive therapy. DXM with concentrations up to 100 mg mL−1 in olive oil are encapsulated while encapsulation efficiency remains over 95% after 15 days. Internalization of NCs by non-parenchymal murine liver cells significantly reduces the release of inflammatory cytokines, indicating an effective suppression of inflammatory response of liver macrophages. Fluorescent and magnetic labeling of the NCs allows for monitoring their intracellular trafficking and biodegradation. Controlled interaction with blood proteins and good colloidal stability in blood plasma are achieved via PEGylation of the NCs. Specific proteins responsible for stealth effect, such as apolipoprotein A-I, apolipoprotein A-IV, and clusterin, are present in large amounts on the PEGylated NCs. In vivo biodistribution investigations prove an efficient accumulation of NCs in the liver, underlining the suitability of the SiO2 NCs as a dexamethasone carrier for treating inflammatory liver diseases.Fil: Jiang, Shuai. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Prozeller, Domenik. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Pereira, Jorge. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Simon, Johanna. Max-Planck-Institut für Polymerforschung; Alemania. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Han, Shen. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Wirsching, Sebastian. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Fichter, Michael. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Mottola, Milagro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Lieberwirth, Ingo. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Morsbach, Svenja. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Mailänder, Volker. Max-Planck-Institut für Polymerforschung; Alemania. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Gehring, Stephan. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Crespy, Daniel. Max-Planck-Institut für Polymerforschung; Alemania. Vidyasirimedhi Institute of Science and Technology; TailandiaFil: Landfester, Katharina. Max-Planck-Institut für Polymerforschung; Alemani

Interest representation in the EU: an open and structured dialogue?

Since 1992, the European Commission has sought to build ‘An Open and Structured Dialogue’ with interest groups, and since 2001 a broader ‘Dialogue with Civil Society’. A core feature of this dialogue involves instruments of transparency, and pluralism, with funding to ensure the presence of a wide range of voices. Consultation procedures provide for a ‘marketplace of ideas’ which simulate political competition and contestation, with a ‘voice but not a vote’, and which are supposed to provide for answerability by the European Commission for its policy choices. The European Commission also selects its allies to support its regulatory proposals, with NGOs frequent allies as well as firms and business sectors supporting higher standards. The EU’s fragmented decision-making system helps to provide a naturally pluralist environment, although some recent research suggests that NGOs are more likely to be successful in securing their policy goals than business organizations. NGOs work mostly in coalitions, with the size of coalition a factor in lobbying success. The saliency of issues is another substantial feature of variation in lobbying success and where NGOs can raise the contention of issues they can bring wider participation in EU issues

Southern Europeans in France: Invisible Migrants?

France fared relatively well at the start of the current economic crisis, but has experienced low economic growth and high unemployment rates in the recent years. As a result it has been a less popular destination with Southern Europeans and EU migrants in general in search of economic opportunities. Although their numbers have increased and represent a growing proportion of recent flows to France, they remain low compared to numbers observed in Germany and the UK. Despite this statistical reality, EU mobility and more generally the role of the EU in economic and social policy have been at the forefront of debates in France since the start of the 2000s, thus well before the start of the crisis. These debates have focused on two populations – the Roma and posted workers – with both groups being portrayed as threats to the French welfare state. Although posted workers are not migrants, according to official EU definitions, their characteristics and experiences are similar to other groups of temporary migrant workers. Southern Europeans account for an increasing number of posted workers, and although they have not been the primary nationalities targeted in discussions concerning this issue, the debates and policy changes introduced in the recent years concern them as well. Moreover, we argue that the focusing of political debates on other populations in France has contributed to the relative invisibility of Southern European immigrants in this country

Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2)

Green tea, mainly through its constituents epigallocatechin gallate, epigallocatechin, epicatechin gallate and epicatechin, has demonstrated anticarcinogenic activity in several animal models, including those for skin, lung and gastro-intestinal tract cancer, although less is known about colorectal cancer. Quercetin, the major flavonoid present in vegetables and fruit, exerts potential anticarcinogenic effects in animal models and cell cultures, but less is known about quercetin glucosides. The objectives of this study were to investigate (i) the antioxidant activity of the phenolic compounds epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside; (ii) the cytotoxicity of different concentrations of epicatechin, epigallocatechin gallate, and gallic acid; (iii) the cellular uptake of epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside and (iv) their effect on the cell cycle. Human colon adenocarcinoma cells were used as experimental model. The results of this study indicate that all dietary flavonoids studied (epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside) show a significant antioxidant effect in a chemical model system, but only epigallocatechin gallate or gallic acid are able to interfere with the cell cycle in Caco2 cell lines. These data suggest that the antioxidant activity of flavonoids is not related to the inhibition of cellular growth. From a structural point of view, the galloyl moiety appears to be required for both the antioxidant and the antiproliferative effects