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.

Effect of surface coating on the biodistribution profile of gold nanoparticles in the rat

“…injection in rat [6,7] and mouse [8][9][10]. The bioavailability of orally administered AuNPs has also been studied in these animal models [10][11][12]. These studies have shown that size is one of the major determinants of biodistribution [7,9,13].…”

Biomolecular coronas provide the biological identity of nanosized materials

“…Biomolecules that are not replaced would serve as a corona 'memory' of the nanoparticle's previous environment. Therefore the corona composition could potentially depend not only on the current environment of the nanoparticle, but on all environments it has moved through 26,27 . Figure 2 illustrates this concept for inhaled nanoparticles carrying typical lung surfactant proteins, and other membrane components, when they reach the blood circulation 28,29 .…”

Synthesis, characterization and evaluation of in vitro toxicity in hepatocytes of linear polyesters with varied aromatic and aliphatic co-monomers

“…Therefore, it is important to elucidate the uptake pattern of the polyester NPs, particularly in hepatic cell lines, as it is well established that the liver is a site of accumulation for many nanoparticles following exposure via various routes (e.g. intravenous injection, ingestion, inhalation/intratracheal instillation) [34,35,37]. The uptake of coated and uncoated P02 NPs in C3A cells suggested that the NPs were taken up by the cells in a time and concentration dependent manner.…”

“…Hepatocytes were selected as the liver is the primary site of nanoparticle accumulation following exposure via different routes (e.g. intratracheal instillation, ingestion, intravenous injection), and existing evidence suggests that C3A cells respond similarly to primary human hepatocytes [34][35][36][37]. The internalization of coated and uncoated polymer nanoparticles by hepatocytes was assessed over time, and their effects on cell viability evaluated using three assays; Alamar Blue, Neutral Red, and 5-CFDA-AM [5-carboxyfluorescein diacetate, acetoxymethyl ester] CFDA-AM.…”