Search results for: Vasile Gheorghita Gaitan

Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

Abstract:

Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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Authors: Jesus Carretero, Mario Vasile, Javier Garcia-Blas, Felix Garcia-Carballeira

Abstract:

Supporting cross-border secure and reliable exchange of data and documents and to promote data interoperability is critical for Europe to enhance sector (like eFinance, eJustice and eHealth). This work presents the status and results of the European Project MADE, a Research Project funded by Connecting Europe facility Programme, to provide secure e-invoicing and e-document exchange systems among Europe countries in compliance with the eIDAS Regulation (Regulation EU 910/2014 on electronic identification and trust services). The main goal of MADE is to develop six new AS4 Access Points and SMP in Europe to provide secure document exchanges using the eDelivery DSI (Digital Service Infrastructure) amongst both private and public entities. Moreover, the project demonstrates the feasibility and interest of the solution provided by providing several months of interoperability among the providers of the six partners in different EU countries. To achieve those goals, we have followed a methodology setting first a common background for requirements in the partner countries and the European regulations. Then, the partners have implemented access points in each country, including their service metadata publisher (SMP), to allow the access to their clients to the pan-European network. Finally, we have setup interoperability tests with the other access points of the consortium. The tests will include the use of each entity production-ready Information Systems that process the data to confirm all steps of the data exchange. For the access points, we have chosen AS4 instead of other existing alternatives because it supports multiple payloads, native web services, pulling facilities, lightweight client implementations, modern crypto algorithms, and more authentication types, like username-password and X.509 authentication and SAML authentication. The main contribution of MADE project is to open the path for European companies to use eDelivery services with cross-border exchange of electronic documents following PEPPOL (Pan-European Public Procurement Online) based on the e-SENS AS4 Profile. It also includes the development/integration of new components, integration of new and existing logging and traceability solutions and maintenance tool support for PKI. Moreover, we have found that most companies are still not ready to support those profiles. Thus further efforts will be needed to promote this technology into the companies. The consortium includes the following 9 partners. From them, 2 are research institutions: University Carlos III of Madrid (Coordinator), and Universidad Politecnica de Valencia. The other 7 (EDICOM, BIZbrains, Officient, Aksesspunkt Norge, eConnect, LMT group, Unimaze) are private entities specialized in secure delivery of electronic documents and information integration brokerage in their respective countries. To achieve cross-border operativity, they will include AS4 and SMP services in their platforms according to the EU Core Service Platform. Made project is instrumental to test the feasibility of cross-border documents eDelivery in Europe. If successful, not only einvoices, but many other types of documents will be securely exchanged through Europe. It will be the base to extend the network to the whole Europe. This project has been funded under the Connecting Europe Facility Agreement number: INEA/CEF/ICT/A2016/1278042. Action No: 2016-EU-IA-0063.

Keywords: security, e-delivery, e-invoicing, e-delivery, e-document exchange, trust

Procedia PDF Downloads 225