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      Models for oral uptake of nanoparticles in consumer products

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          Abstract

          Presently, many consumer products contain nano-sized materials (NMs) to improve material properties, product quality and ease of use. NMs in food additives and in cosmetic articles (e.g., tooth paste) may be taken up by the oral route. As adverse effects of environmental nanoparticles, like ultrafine particles, have been reported, consumers worry about potential risks when using products containing NMs. The review focuses on metal and metal oxide NMs as common additives in tooth paste and in food industry and exposure by the oral route. Testing of NMs for oral exposure is very complex because differences in the diet, in mucus secretion and composition, in pH, in gastrointestinal transit time and in gastrointestinal flora influence NM uptake. Acellular (mucus, saliva) and epithelial layer of the orogastrointestinal barrier are described. Expected exposure doses, interaction of the NMs with mucus and permeation through the epithelium as well as in vivo data are mentioned. The role of in vitro models for the study of parameters relevant for ingested NMs is discussed.

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          Most cited references104

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          Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm.

          Nanomaterial properties differ from those bulk materials of the same composition, allowing them to execute novel activities. A possible downside of these capabilities is harmful interactions with biological systems, with the potential to generate toxicity. An approach to assess the safety of nanomaterials is urgently required. We compared the cellular effects of ambient ultrafine particles with manufactured titanium dioxide (TiO2), carbon black, fullerol, and polystyrene (PS) nanoparticles (NPs). The study was conducted in a phagocytic cell line (RAW 264.7) that is representative of a lung target for NPs. Physicochemical characterization of the NPs showed a dramatic change in their state of aggregation, dispersibility, and charge during transfer from a buffered aqueous solution to cell culture medium. Particles differed with respect to cellular uptake, subcellular localization, and ability to catalyze the production of reactive oxygen species (ROS) under biotic and abiotic conditions. Spontaneous ROS production was compared by using an ROS quencher (furfuryl alcohol) as well as an NADPH peroxidase bioelectrode platform. Among the particles tested, ambient ultrafine particles (UFPs) and cationic PS nanospheres were capable of inducing cellular ROS production, GSH depletion, and toxic oxidative stress. This toxicity involves mitochondrial injury through increased calcium uptake and structural organellar damage. Although active under abiotic conditions, TiO2 and fullerol did not induce toxic oxidative stress. While increased TNF-alpha production could be seen to accompany UFP-induced oxidant injury, cationic PS nanospheres induced mitochondrial damage and cell death without inflammation. In summary, we demonstrate that ROS generation and oxidative stress are a valid test paradigm to compare NP toxicity. Although not all materials have electronic configurations or surface properties to allow spontaneous ROS generation, particle interactions with cellular components are capable of generating oxidative stress.
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            Barrier properties of mucus.

            Mucus is tenacious. It sticks to most particles, preventing their penetration to the epithelial surface. Multiple low-affinity hydrophobic interactions play a major role in these adhesive interactions. Mucus gel is also shear-thinning, making it an excellent lubricant that ensures an unstirred layer of mucus remains adherent to the epithelial surface. Thus nanoparticles (NP) must diffuse readily through the unstirred adherent layer if they are to contact epithelial cells efficiently. This article reviews some of the physiological and biochemical properties that form the mucus barrier. Capsid viruses can diffuse through mucus as rapidly as through water and thereby penetrate to the epithelium even though they have to diffuse 'upstream' through mucus that is being continuously secreted. These viruses are smaller than the mucus mesh spacing, and have surfaces that do not stick to mucus. They form a useful model for developing NP for mucosal drug delivery.
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              Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals.

              In addition to metabolic differences, the anatomical, physiological, and biochemical differences in the gastrointestinal (G.I.) tract of the human and common laboratory animals can cause significant variation in drug absorption from the oral route. Among the physiological factors, pH, bile, pancreatic juice, and mucus and fluid volume and content can modify dissolution rates, solubility, transit times, and membrane transport of drug molecules. The microbial content of the G.I. tract can significantly affect the reductive metabolism and enterohepatic circulation of drugs and colonic delivery of formulations. The transit time of dosage forms can be significantly different between species due to different dimensions and propulsive activities of the G.I. tract. The lipid/protein composition of the enterocyte membrane along the G.I. tract can alter binding and passive, active, and carrier-mediated transport of drugs. The location and number of Peyer's patches can also be important in the absorption of large molecules and particulate matter. While small animals, rats, mice, guinea pigs, and rabbits, are most suitable for determining the mechanism of drug absorption and bioavailability values from powder or solution formulations, larger animals, dogs, pigs, and monkeys, are used to assess absorption from formulations. The understanding of physiological, anatomical, and biochemical differences between the G.I. tracts of different animal species can lead to the selection of the correct animal model to mimic the bioavailability of compounds in the human. This article reviews the anatomical, physiological, and biochemical differences between the G.I. tracts of humans and commonly used laboratory animals.
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                Author and article information

                Journal
                Toxicology
                Toxicology
                Toxicology
                Elsevier
                0300-483X
                1879-3185
                27 January 2012
                27 January 2012
                : 291
                : 1-3
                : 10-17
                Affiliations
                [a ]Center for Medical Research, Medical University of Graz, Austria
                [b ]Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University of Graz, Austria
                [c ]Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University of Graz, Austria
                Author notes
                [* ]Corresponding author at: Center for Medical Research, Medical University Graz, Stiftingtalstr. 24, A-8010 Graz, Austria. Tel.: +43 31638573011; fax: +43 31638573009. eleonore.froehlich@ 123456medunigraz.at
                Article
                TOX50881
                10.1016/j.tox.2011.11.004
                3273702
                22120540
                23348b46-2b51-4906-b4a3-0646308568ca
                © 2012 Elsevier Ireland Ltd.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 12 October 2011
                : 7 November 2011
                : 9 November 2011
                Categories
                Review

                Toxicology
                nanomaterials,titanium dioxide,epithelial barriers,silver,consumer products,silicon oxide
                Toxicology
                nanomaterials, titanium dioxide, epithelial barriers, silver, consumer products, silicon oxide

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