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      Deposition and biokinetics of inhaled nanoparticles

      review-article
      1 , , 2 , 3
      Particle and Fibre Toxicology
      BioMed Central

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          Abstract

          Particle biokinetics is important in hazard identification and characterization of inhaled particles. Such studies intend to convert external to internal exposure or biologically effective dose, and may help to set limits in that way. Here we focus on the biokinetics of inhaled nanometer sized particles in comparison to micrometer sized ones.

          The presented approach ranges from inhaled particle deposition probability and retention in the respiratory tract to biokinetics and clearance of particles out of the respiratory tract. Particle transport into the blood circulation (translocation), towards secondary target organs and tissues (accumulation), and out of the body (clearance) is considered. The macroscopically assessed amount of particles in the respiratory tract and secondary target organs provides dose estimates for toxicological studies on the level of the whole organism. Complementary, microscopic analyses at the individual particle level provide detailed information about which cells and subcellular components are the target of inhaled particles. These studies contribute to shed light on mechanisms and modes of action eventually leading to adverse health effects by inhaled nanoparticles.

          We review current methods for macroscopic and microscopic analyses of particle deposition, retention and clearance. Existing macroscopic knowledge on particle biokinetics and microscopic views on particle organ interactions are discussed comparing nanometer and micrometer sized particles. We emphasize the importance for quantitative analyses and the use of particle doses derived from real world exposures.

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          Most cited references81

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          Polymer conjugates as anticancer nanomedicines.

          The transfer of polymer-protein conjugates into routine clinical use, and the clinical development of polymer-anticancer-drug conjugates, both as single agents and as components of combination therapy, is establishing polymer therapeutics as one of the first classes of anticancer nanomedicines. There is growing optimism that ever more sophisticated polymer-based vectors will be a significant addition to the armoury currently used for cancer therapy.
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            The unbiased estimation of number and sizes of arbitrary particles using the disector.

            D Sterio (1984)
            A three-dimensional counting rule and its integral test system, the disector, for obtaining unbiased estimates of the number of arbitrary particles in a specimen is presented. Used in combination with ordinary and recently developed stereological methods unbiased estimates of various mean particle sizes and the variance of particle volume are obtainable on sets of two parallel sections with a known separation. The same principle allows the unbiased estimation of the distribution of individual particle volumes in sets of serial sections.
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              Association of fine particulate matter from different sources with daily mortality in six U.S. cities.

              Previously we reported that fine particle mass (particulate matter [less than and equal to] 2.5 microm; PM(2.5)), which is primarily from combustion sources, but not coarse particle mass, which is primarily from crustal sources, was associated with daily mortality in six eastern U.S. cities (1). In this study, we used the elemental composition of size-fractionated particles to identify several distinct source-related fractions of fine particles and examined the association of these fractions with daily mortality in each of the six cities. Using specific rotation factor analysis for each city, we identified a silicon factor classified as soil and crustal material, a lead factor classified as motor vehicle exhaust, a selenium factor representing coal combustion, and up to two additional factors. We extracted daily counts of deaths from National Center for Health Statistics records and estimated city-specific associations of mortality with each source factor by Poisson regression, adjusting for time trends, weather, and the other source factors. Combined effect estimates were calculated as the inverse variance weighted mean of the city-specific estimates. In the combined analysis, a 10 microg/m(3) increase in PM(2.5) from mobile sources accounted for a 3.4% increase in daily mortality [95% confidence interval (CI), 1.7-5.2%], and the equivalent increase in fine particles from coal combustion sources accounted for a 1.1% increase [CI, 0.3-2.0%). PM(2.5) crustal particles were not associated with daily mortality. These results indicate that combustion particles in the fine fraction from mobile and coal combustion sources, but not fine crustal particles, are associated with increased mortality.
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                Author and article information

                Journal
                Part Fibre Toxicol
                Particle and Fibre Toxicology
                BioMed Central
                1743-8977
                2010
                20 January 2010
                : 7
                : 2
                Affiliations
                [1 ]Institute of Anatomy, University of Bern, Baltzerstrasse 2, CH-3000 Bern 9, Switzerland
                [2 ]Comprehensive Pneumology Center, Institute of Lung Biology and Disease and Focus-Network Nanoparticles and Health, Helmholtz Center Munich, Munich, Germany
                [3 ]German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, D-85764 Neuherberg/Munich, Germany
                Article
                1743-8977-7-2
                10.1186/1743-8977-7-2
                2826283
                20205860
                0256781d-382a-45bb-9139-285f08d356e6
                Copyright ©2010 Geiser and Kreyling; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 August 2009
                : 20 January 2010
                Categories
                Review

                Toxicology
                Toxicology

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