Data Harmonisation Put into Practice by the HUMBOLDT Project

Data harmonisation is a key prerequisite for an efficient and meaningful combination of heterogeneous information in cross-border applications and spatial data infrastructures. This is also the main objective of the INSPIRE Directive which has entered its implementation phase. Data Specifications for INSPIRE Annex I data themes have been published containing harmonised, pan-European data models and a number of other requirements. Data providers across Europe face the challenge of transforming their legacy data to comply with these Data Specifications. This paper presents results of the European project HUMBOLDT. Data harmonisation requirements identified in nine scenarios covering a wide range of application domains and using heterogeneous data from a number of European countries are illustrated. Processes required to achieve data harmonisation are described from an application point of view. The open-source software framework for data harmonisation and services integration developed in the project is introduced and its use in two application scenarios is demonstrated

Size and surface charge of gold nanoparticles determine absorption across intestinal barriers and accumulation in secondary target organs after oral administration

It is of urgent need to identify the exact physico-chemical characteristics which allow maximum uptake and accumulation in secondary target organs of nanoparticulate drug delivery systems after oral ingestion. We administered radiolabelled gold nanoparticles in different sizes (1.4-200 nm) with negative surface charge and 2.8 nm nanoparticles with opposite surface charges by intra-oesophageal instillation into healthy adult female rats. The quantitative amount of the particles in organs, tissues and excrements was measured after 24 h by gamma-spectroscopy. The highest accumulation in secondary organs was mostly found for 1.4 nm particles; the negatively charged particles were accumulated mostly more than positively charged particles. Importantly, 18 nm particles show a higher accumulation in brain and heart compared to other sized particles. No general rule accumulation can be made so far. Therefore, specialized drug delivery systems via the oral route have to be individually designed, depending on the respective target organ

Data harmonisation put into practice by the HUMBOLDT project

Data harmonisation is a key prerequisite for an efficient and meaningful combination of heterogeneous information in cross-border applications and spatial data infrastructures. This is also the main objective of the INSPIRE Directive which has entered its implementation phase. Data Specifications for INSPIRE Annex I data themes have been published containing harmonised, pan- European data models and a number of other requirements. Data providers across Europe face the challenge of transforming their legacy data to comply with these Data Specifications. This paper presents results of the European project HUMBOLDT. Data harmonisation requirements identified in nine scenarios covering a wide range of application domains and using heterogeneous data from a number of European countries are illustrated. Processes required to achieve data harmonisation are described from an application point of view. The open-source software framework for data harmonisation and services integration developed in the project is introduced and its use in two application scenarios is demonstrated

Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration

Gold nanoparticles (GNP) provide many opportunities in imaging, diagnostics, and therapies of nanomedicine. Hence, their biokinetics in the body are prerequisites for specific tailoring of nanomedicinal applications and for a comprehensive risk assessment. We administered (198)Au-radio-labelled monodisperse, negatively charged GNP of five different sizes (1.4, 5, 18, 80, and 200 nm) and 2.8 nm GNP with opposite surface charges by intravenous injection into rats. After 24h, the biodistribution of the GNP was quantitatively measured by gamma-spectrometry. The size and surface charge of GNP strongly determine the biodistribution. Most GNP accumulated in the liver increased from 50% of 1.4 nm GNP to >99% of 200 nm GNP. In contrast, there was little size-dependent accumulation of 18-200 nm GNP in most other organs. However, for GNP between 1.4 nm and 5 nm, the accumulation increased sharply with decreasing size; i.e. a linear increase with the volumetric specific surface area. The differently charged 2.8 nm GNP led to significantly different accumulations in several organs. We conclude that the alterations of accumulation in the various organs and tissues, depending on GNP size and surface charge, are mediated by dynamic protein binding and exchange. A better understanding of these mechanisms will improve drug delivery and dose estimates used in risk assessment

Air-Blood Barrier Translocation of Tracheally Instilled Gold Nanoparticles Inversely Depends on Particle Size

Gold nanoparticles (AuNP) provide many opportunities in imaging, diagnostics, and therapy in nanomedicine. For the assessment of AuNP biokinetics, we intratracheally instilled into rats a suite of 198Au-radio-labeled monodisperse, well-characterized, negatively charged AuNP of five different sizes (1.4, 2.8, 5, 18, 80, 200 nm) and 2.8 nm AuNP with positive surface charges. At 1, 3, and 24 h, the biodistribution of the AuNP was quantitatively measured by gamma-spectrometry to be used for comprehensive risk assessment. Our study shows that as AuNP get smaller, they are more likely to cross the air–blood barrier (ABB) depending strongly on the inverse diameter d–1 of their gold core, i.e., their specific surface area (SSA). So, 1.4 nm AuNP (highest SSA) translocated most, while 80 nm AuNP (lowest SSA) translocated least, but 200 nm particles did not follow the d–1 relation translocating significantly higher than 80 nm AuNP. However, relative to the AuNP that had crossed the ABB, their retention in most of the secondary organs and tissues was SSA-independent. Only renal filtration, retention in blood, and excretion via urine further declined with d–1 of AuNP core. Translocation of 5, 18, and 80 nm AuNP is virtually complete after 1 h, while 1.4 nm AuNP continue to translocate until 3 h. Translocation of negatively charged 2.8 nm AuNP was significantly higher than for positively charged 2.8 nm AuNP. Our study shows that translocation across the ABB and accumulation and retention in secondary organs and tissues are two distinct processes, both depending specifically on particle characteristics such as SSA and surface charge