title: 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.
authors.affiliation: Comprehensive Pneumology Center - Institute of Lung Biology and Disease and Focus Network NP and Health, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. carsten.schleh@helmholtz-muenchen.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Schleh
authors.forename: Manuela
authors.initials: M
authors.lastname: Semmler-Behnke
authors.forename: Jens
authors.initials: J
authors.lastname: Lipka
authors.forename: Alexander
authors.initials: A
authors.lastname: Wenk
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hirn
authors.forename: Martin
authors.initials: M
authors.lastname: Schäffler
authors.forename: Günter
authors.initials: G
authors.lastname: Schmid
authors.forename: Ulrich
authors.initials: U
authors.lastname: Simon
authors.forename: Wolfgang G
authors.initials: WG
authors.lastname: Kreyling
mesh_terms: D000284:Administration, Oral; D000818:Animals; D005260:Female; D005766:Gastrointestinal Contents / Q000737:chemistry; D041981:Gastrointestinal Tract / Q000737:chemistry / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D011921:Rats, Inbred WKY; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: C523286:1,3-bis(5-amino-5-carboxypentyl)-1H-imidazolium; D007093:Imidazoles; D008239:Lysine