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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - HYMADE (Hybrid Drug Delivery Systems upon Mesoporous Materials, Self Assembled Therapeutics and Virosomes)

Teaser

Summary

HYMADE focuses on the development of capsules and engineered colloidal particles for drug delivery combining mesoporous colloids, the Layer by Layer (LbL) technique and virosomes. The capsules and particles have potential applications in cancer and inflammatory diseases such as rheumatoid arthritis and uveitis. The project is based on the secondments of Early Stage and Experienced Researchers and networking and training activities between European and non-European academic institutions. HYMADE aims to profit from the combination of hybrid materials to fabricate advanced drug delivery systems with controlled release and targeting efficiency of biological entities. It also aims to gain understanding of the self-assembly process of hybrid materials and the transport properties of the drug delivery systems. The biological fate, drug release, degradation and therapeutical efficiency of the drug delivery systems are studied in vitro and in vivo with state of the art imaging techniques. To achieve these goals, we have gathered an international multidisciplinary team including scientists at the forefront of Material Science, Self-assembly, Physics, Chemistry, Biophysics and Imaging from Germany, Austria, France and Spain on the European side and from USA, Argentina and Armenia on the non-European side. Seconded researchers will have a unique opportunity for personal and scientific development, which will enhance their career perspectives and generate highly skillful personnel at the interface of the materials and biomedical sciences.

Work performed

During the first 2 years, work has mainly focused on WP1: synthesis and fabrication of building block components, and WP2: integration of nanoscale components into drug delivery systems. Work has also been performed related to WP3: Self assembly mechanism and nano and micro scale characterisation and WP4: Transport phenomena.

Worpackage 1: Synthesis and fabrication of building block components
The main scientific object is the fabrication of polymers, nanoparticles, nanorods, mesoporous solids, virosomes with proper architecture and functionality that will be the basis of the subsequent self-assembly for the fabrication of drug delivery assemblies, as well as their characterisation with regard to functionality and assembly. This objective has been achieved as well as the specific objectives of the WP: 1) Synthesis of polymers, nanoparticles; 2) Synthesis of mesoporous solids; 3) Fabrication of virosomes carrying sensor molecules. A battery of materials was prepared during the first year through the different secondments that will be used as nanoscale components. All the tasks considered in WP 1 have been tackled in the first year of the project.
Workpackage 2: Integration of nanoscale components into drug delivery systems.
The main objective is the integration of polymers, nanoparticles, nucleic acids, antibodies, lipids and virosomes to fabricate drug delivery systems. The scientific work to achieve this objective is in progress as well as the work to achieve the specific objectives proposed: 1) Fabricate capsules and LbL coated colloids including therapeutics as layer constituents; 2) Fabricate hybrid assemblies on the basis of virus nanoparticles/virosomes, lipid layers and polyelectrolytes on top of colloidal particles; 3) Coat mesoporous colloidal particles with polyelectrolyte multilayers.
Workpackage 3: Self-assembly mechanism and nano and micro scale characterisation
The aim is to study the properties and functionality of the assemblies that result from the nanoscale organisation of the individual components. The properties targeted are relevant for the application of the assemblies in drug delivery and for their optimisation. One specific objective was addressed: Study the mechanism of self-assembly of the fabricated assemblies. To this end, we have implemented the use of Optical Waveguide Spectroscopy (OWS) to elucidate the physicochemical variables that govern the self-assembly of polyelectrolyte multilayers into mesoporous thin films. During this period seconded researchers at AIT worked on elucidating the Interfacial chemical changes induced by enzymatic processes. They studied the variation in local pH induced by enzymatic processes occurring in enzyme-containing interfacial macromolecular assemblies. They employed graphene field effect transistor (gFETs) to sensitively monitor subtle interfacial pH occurring in layer-by-layer assemblies during enzymatic reactions. Researchers at UPMC worked on understanding the interfacial dynamic of mesoporous silica vectors when they are dispersed in real simulated and biological environment. They also studied the dissolution kinetic of thin films of composition and thickness similar to those of silica-based therapeutic vectors. They also synthesized and studied the synthesis of new lanthanide-based Metal Organic Frameworks. Luminescent and magnetic properties were studied and used as a first approach for sensing of common chemicals.
Workpackage 4: Transport phenomena
The aim of this WP is the study of transport phenomena. We studied 1)Transport properties of mesoporous materials modified with polyelectrolyte multilayers and the influence of the self-assembly conditions on the perm-selective properties of the nanocomposite interfacial architectures; 2) the effective/local pH changes taking place inside polyelectrolyte multilayers containing urease into layered nanostructure. The purpose of these experiments was to validate and quantify the potential use enzymatic process as

Final results

The general strategy of HYMADE is to promote scientific and technological excellence, as well as strong internal and external dissemination by the consortium members. The project website is accessible since April 2015 and is regularly updated with information on the project overview, objectives, and information about partners, events, publications and related links. Two articles have been published in peer-reviewed journals: Biosensors and nature communications by Reiner et al. (2016) and Liu et al. (2016) respectively, both with open accessibility. Results framed within the project were presented at the XIIth Annual meeting of the Argentinian crystallographic association. Several thematic workshops were organised as well, in Paris (France), Vienna (Austria), Hirschegg (Austria) and Outreach activities took place in several European cities (San SebastiÃ¡n, Vienna).