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Scheuerle R.L.,University of Cambridge | Bruggraber S.F.A.,Biomineral Research Group | Gerrard S.E.,University of Cambridge | Kendall R.A.,University College London | And 2 more authors.
PLoS ONE | Year: 2017

Zinc delivery from a nipple shield delivery system (NSDS), a novel platform for administering medicines to infants during breastfeeding, was characterised using a breastfeeding simulation apparatus. In this study, human milk at flow rates and pressures physiologically representative of breastfeeding passed through the NSDS loaded with zinc-containing rapidly disintegrating tablets, resulting in release of zinc into the milk. Inductively coupled plasma optical emission spectrometry was used to detect the zinc released, using a method that does not require prior digestion of the samples and that could be applied in other zinc analysis studies in breast milk. Four different types of zinc-containing tablets with equal zinc load but varying excipient compositions were tested in the NSDS in vitro. Zinc release measured over 20 minutes ranged from 32-51% of the loaded dose. Total zinc release for sets tablets of the same composition but differing hardness were not significantly different from one another with P = 0.3598 and P = 0.1270 for two tested pairs using unpaired t tests with Welch's correction. By the same test total zinc release from two sets of tablets having similar hardness but differing composition were also not significantly significant with P = 0.2634. Future zinc tablet composition and formulation optimisation could lead to zinc supplements and therapeutics with faster drug release, which could be administered with the NSDS during breastfeeding. The use of the NSDS to deliver zinc could then lead to treatment and prevention of some of the leading causes of child mortality, including diarrheal disease and pneumonia. © 2017 Scheuerle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Gerloff K.,IUF Leibniz Research Institute for Environmental Medicine | Gerloff K.,University of Queensland | Pereira D.I.A.,Biomineral Research Group | Faria N.,Biomineral Research Group | And 6 more authors.
Nanotoxicology | Year: 2013

Novel aspects of engineered nanoparticles offer many advantages for optimising food products and packaging. However, their potential hazards in the gastrointestinal tract require further investigation. We evaluated the toxic and inflammatory potential of two types of particles that might become increasingly relevant to the food industry, namely SiO2 and ZnO. The materials were characterised for their morphology, oxidant generation and hydrodynamic behaviour. Cytotoxicity and interleukin-8 mRNA and protein expression were evaluated in human intestinal Caco-2 cells. Particle pretreatment under simulated gastric and intestinal pH conditions resulted in reduced acellular ROS formation but did not influence cytotoxicity (WST-1 assay) or IL-8 expression. However, the differentiation status of the cells markedly determined the cytotoxic potency of the particles. Further research is needed to determine the in vivo relevance of our current observations regarding the role of particle aggregation and the stage of intestinal epithelial cell differentiation in determining the hazards of ingested particles. © 2013 Informa UK, Ltd.


Faria N.,Biomineral Research Group | Pereira D.,Biomineral Research Group | Mergler B.,Biomineral Research Group | Powell J.,Biomineral Research Group
Proceedings of the IEEE Conference on Nanotechnology | Year: 2011

We report on (a) a novel procedure to dope ferric oxide primary particles with GRAS ligands (b) their characterization and stability in cell culture solution (c) their uptake and utilization by gut cells in culture and (d) their delivery to human volunteers. Overall, these materials are cheap to manufacture and show promise for safe and efficient oral iron delivery to help ease the global burden of iron deficiency anemia. © 2011 IEEE.


Powell J.,Biomineral Research Group | Pele L.,Biomineral Research Group
Proceedings of the IEEE Conference on Nanotechnology | Year: 2011

Gastrointestinal exposure to nanoparticles and microparticles appears to be a normal occurrence and, likely, is something that humans have faced throughout evolution. In fact mechanisms have evolved to utilise, beneficially, at least one dietary nanoparticle, namely ferritin. This is the storage form of iron and is ingested in both the meat-based and plant-based aspects of the diet. Additionally, however, we propose that beneficial nano/microparticles may actively from in situ in the gut lumen. Of special note is calcium phosphate. The secretion of calcium and phosphate ions in the succus entericus (gut secretion fluid) leads to co-precipitation of particles. These could trap organic luminal molecules and then cross the epithelial barrier, especially at the M cell portal, as an entire conjugate. Cellular dissolution of the conjugate would release calcium ions and phosphate ions as well as the organic molecules (typically antigens) being carried and thus allow the immune system to survey the luminal contents. Our group is working to prove this hypothesis. Additionally, however, the M cell portal will be exposed to man-made particles such as silicates and titanium dioxide that enter the diet through ingestion of processed foods, pharmaceuticals, nutraceuticals and toothpaste. These particles are scavenged- probably via the mechanism intended for endogenously forming calcium phosphate- and can be seen to accumulate in the cells (macrophages) at the base of human intestinal lymphoid aggregates. They are likely to also adsorb to their surface luminal organic molecules, which they may subsequently release following cellular uptake. But unlike calcium phosphate, these man-made exogenous particles will not dissolve in the cell lysosome. So whether they then provide aggressive, persistent signals for cellular responses remains to be elucidated. Again, our group has a particular interest in the idea that certain genetically-susceptible individuals may have pro-inflammatory responses to these exogenous particles. © 2011 IEEE.


Ivask A.,Estonian National Institute of Chemical Physics and Biophysics | Kurvet I.,Estonian National Institute of Chemical Physics and Biophysics | Kasemets K.,Estonian National Institute of Chemical Physics and Biophysics | Blinova I.,Estonian National Institute of Chemical Physics and Biophysics | And 11 more authors.
PLoS ONE | Year: 2014

The concept of nanotechnologies is based on size-dependent properties of particles in the 1-100 nm range. However, the relation between the particle size and biological effects is still unclear. The aim of the current paper was to generate and analyse a homogenous set of experimental toxicity data on Ag nanoparticles (Ag NPs) of similar coating (citrate) but of 5 different primary sizes (10, 20, 40, 60 and 80 nm) to different types of organisms/cells commonly used in toxicity assays: bacterial, yeast and algal cells, crustaceans and mammalian cells in vitro. When possible, the assays were conducted in ultrapure water to minimise the effect of medium components on silver speciation. The toxic effects of NPs to different organisms varied about two orders of magnitude, being the lowest (∼0.1 mg Ag/L) for crustaceans and algae and the highest (∼26 mg Ag/L) for mammalian cells. To quantify the role of Ag ions in the toxicity of Ag NPs, we normalized the EC50 values to Ag ions that dissolved from the NPs. The analysis showed that the toxicity of 20-80 nm Ag NPs could fully be explained by released Ag ions whereas 10 nm Ag NPs proved more toxic than predicted. Using E. coli Ag-biosensor, we demonstrated that 10 nm Ag NPs were more bioavailable to E. coli than silver salt (AgNO3). Thus, one may infer that 10 nm Ag NPs had more efficient cell-particle contact resulting in higher intracellular bioavailability of silver than in case of bigger NPs. Although the latter conclusion is initially based on one test organism, it may lead to an explanation for "size-dependent" biological effects of silver NPs. This study, for the first time, investigated the size-dependent toxic effects of a well-characterized library of Ag NPs to several microbial species, protozoans, algae, crustaceans and mammalian cells in vitro. © 2014 Ivask et al.

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