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

Abstract

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.

Keywords::

• Gold NP
• gavage
• absorption
• gastro-intestinal tract
• in vivo biodistribution

Acknowledgements

We thank Georg Müller (RWTH) for the synthesis and Heidrum Keul (DWI) for the TEM analyses of the 2.8 nm Au particles. We thank Dr Carsten Rudolph from Dr von Hauner Children's Hospital, LMU Munich, for his supports of zeta potential measurements. We also thank Dr Dorothea Alber and Gregor Bukalis from the Helmholtz Zentrum in Berlin for performing the neutron activation of our GNP at the research reactor BER II.

Declaration of interest: This work was partially supported by the German Research Foundation FOR 627, SPP 1313 and PAK 56, the EU-FP6 project Particle-Risk (012912 (NEST)), and the EU FP7 projects NeuroNano (NMP4-SL- 2008-214547), ENPRA (NMP4-SL-2009-228789) as well as InLIveTox (NMP-2008-1.3-2 CP-FP 228625-2) and US-NIH grant HL074022. The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

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