Nanoparticles in the lung : environmental exposure and drug delivery

388 Pages·2015·54.93 MB·English

by  edited by Akira Tsuda

Biomedical Engineering Tsuda
Gehr
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Nanoparticles in the Lung
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Environmental Exposure and Drug Delivery
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Nanoparticles have a physical dimension comparable to the size of p
molecular structures on the cell surface. Therefore, nanoparticles, compared
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when they interact with cells.
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Nanoparticles in the Lung: Environmental Exposure and Drug Delivery t
provides a better understanding of how inhaled nanoparticles behave in i
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and epithelium, translocation across the air–blood tissue barrier, and
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In addition, the book addresses practical considerations for drug delivery
to the respiratory tract, drug and gene delivery in the lungs, and bio-

nanocapsules. It considers the physicochemical, colloidal, and transport t
properties of nanoparticles, and presents cutting-edge research on special h
issues such as dosimetry for in vitro nanotoxicology, nanoparticle deposition
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in the developing lungs, and the potential for nose-to-brain delivery of drugs.

Nanoparticles in the Lung: Environmental Exposure and Drug Delivery
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offers the most updated and comprehensive knowledge of the risks and
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benefits associated with nanoparticle inhalation—to protect humans from
any harmful effects and to explore the utility of nanoparticles as drug
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delivery carriers.
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K14165
ISBN: 978-1-4398-9279-4
90000
9 781439 892794
K14165_COVER_final.indd 1 11/13/14 2:41 PM

Nanoparticles
Lung
in the
Environmental Exposure
and Drug Delivery

Nanoparticles
Lung
in the
Environmental Exposure
and Drug Delivery
Edited by
Akira Tsuda
Harvard University
Cambridge Massachusetts, USA
Peter Gehr
University of Bern
Switzerland
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
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© 2015 by Taylor & Francis Group, LLC
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Version Date: 20141030
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Contents
Foreword .......................................................................................................................................vii
Preface ..............................................................................................................................................ix
Editors ..............................................................................................................................................xi
Contributors .................................................................................................................................xiii
1 Introduction .............................................................................................................................1
Akira Tsuda and Peter Gehr
Section I Gas Phase
2 Deposition ................................................................................................................................5
Akira Tsuda and Frank S. Henry
Section II Airway/Alveolar Surface
3 Interaction with the Lung Surface ....................................................................................21
Peter Gehr and Akira Tsuda
4 Role of the Biomolecule Corona in Nanoparticle Fate and Behavior ........................47
Iseult Lynch
5 Interaction with Alveolar Lining Fluid ...........................................................................73
Vincent Castranova, Dale W. Porter, and Robert R. Mercer
6 Interaction with Lung Macrophages ................................................................................85
Barry Weinberger, Patrick J. Sinko, Jeffrey D. Laskin, and Debra L. Laskin
Section III Crossing Epithelial Cells
7 Interactions with Alveolar Epithelium ..........................................................................107
Farnoosh Fazlollahi, Yong Ho Kim, Arnold Sipos, Zea Borok, Kwang-Jin Kim,
and Edward D. Crandall
8 Mechanistic Aspects of Cellular Uptake .......................................................................133
Lennart Treuel, Xiue Jiang, and Gerd Ulrich Nienhaus
9 Cellular Uptake and Intracellular Trafficking .............................................................147
Barbara Rothen-Rutishauser, Dagmar A. Kuhn, Dimitri Vanhecke, Fabian Herzog,
Alke Petri-Fink, and Martin J.D. Clift
v
vi Contents
Section IV Translocation
10 Translocation across the Air–Blood Tissue Barrier .....................................................169
Fabian Blank, Christophe von Garnier, Peter Gehr, and Barbara Rothen-Rutishauser
11 The Pulmonary Lymphatic System .................................................................................183
Akira Tsuda
12 Translocation and Accumulation in the Body ..............................................................197
Wolfgang G. Kreyling
Section V Drug Delivery to the Respiratory Tract
13 Practical Considerations for Drug Delivery to the Respiratory Tract .....................211
John S. Patton
14 Drug and Gene Delivery in the Lungs ...........................................................................225
Satoshi Uchida, Keiji Itaka, and Kazunori Kataoka
15 Bio-Nanocapsules: Novel Drug Delivery ......................................................................239
Shun’ichi Kuroda
Section VI Special Issues
16 Physicochemical, Colloidal, and Transport Properties...............................................251
Heinrich Hofmann, Lionel Maurizi, Marie-Gabrielle Beuzelin, Usawadee Sakulkhu,
and Vianney Bernau
17 Dosimetry for In Vitro Nanotoxicology: Too Complicated to Consider, Too
Important to Ignore ............................................................................................................267
Joel M. Cohen and Philip Demokritou
18 Potential for Nose-to-Brain Delivery of Drugs ............................................................295
Lisbeth Illum
19 The Developing Lungs ......................................................................................................323
Akira Tsuda and Frank S. Henry
20 Nanotoxicology ...................................................................................................................341
Dominique Balharry, Eva Gubbins, Helinor Johnston, Ali Kermanizadeh, and Vicki Stone
21 Summary ..............................................................................................................................365
Peter Gehr and Akira Tsuda
Foreword
There is no doubt that the topics of nanotechnology and the associated fields of nanomedi-
cine and nanotoxicology have grown dramatically during the past decades. Corporations,
universities, and governments are supporting a rapid growth in research and develop-
ment. We also see substantial numbers of nano-enabled products. Of particular inter-
est are highly engineered nanomaterials, such as quantum dots, carbon nanotubes, and
fullerenes.
At the same time, the words of Solomon in the Book of Ecclesiastes seem appropriate,
“There is nothing new under the sun.” India ink is a stable colloid of carbon nanoparticles
(NPs). Artisans in the ninth century used silver and copper NPs in pottery glazes. Other
familiar examples are tattoo inks, which have many NPs, and especially tobacco smoke.
Intravenously injected radioactive NPs of 198Au colloid were used decades ago to treat liver
cancer. All contain polydisperse particles that have a substantial fraction whose diameter
is less than 100 nm, especially as a function of number.
One can go back even further to when humans discovered fire. Smokes are polydis-
perse aerosols that include NPs, usually defined as being less than 0.1 μm in at least
one dimension. The air pollution field has long recognized the existence of nanosized or
ultrafine particles, sometimes referred to as PM . Important sources of such “uninten-
0.1
tionally produced NPs” include cars, trucks, airplanes, other combustion processes, metal
mining, welding, and smelting, as well as those produced by natural processes such as
forest fires, volcanoes, sea spray, or wind erosion. Atmospheric chemical processes acting
on air pollutants produce NPs following nucleation of extremely small particles, which
then grow by condensation and coagulation. When ingested by alveolar macrophages,
respirable particles, e.g., PM , if they completely dissolve, inevitably progress through a
2.5
NP size range.
This excellent book focuses primarily on the intentional production of NPs, which are
sometimes highly engineered. The universe of technologies, new materials, and products
is vast. There is a pressing need to ask and answer the questions articulated in the many
chapters of this comprehensive volume. As is true for the existence of NPs, there are both
old and new concepts in this book. The familiar saying, “the dose makes the poison,” con-
tinues to be true. We need to understand the temporal relationships of NP concentrations
in relevant organs during and after exposure. This in turn depends on initial deposition,
clearance processes, solubility of the particles, translocation, and overall persistence. For
organs and tissues of interest, we need to know the area under the curve as we describe
concentration versus time.
In contrast, there are many chapters in this volume that discuss topics hitherto ignored
or even unimagined. For example, we are just beginning to describe how the size, shape,
and surface of NPs determine the protein and phospholipid corona, which rapidly envel-
ops nanomaterials in the lungs as molecules from the alveolar lining layer and airway
mucus bind reversibly and irreversibly to NP surfaces. We also need to better under-
stand how that corona then affects the fate of NPs. For example, the protein corona likely
defines the particle affinity for different specific particle receptors on macrophage sur-
faces. Other topics in this book that focus on important unexplored areas are the extent
to which NPs enter the pulmonary lymphatics and the likelihood of NP transport to the
brain via the nose and the olfactory system. Finally, we are just beginning to characterize
vii
viii Foreword
the potential of NP drug delivery to and through the respiratory tract, another important
theme in this book.
Should we be concerned about the hazards of nanomaterials? Is there a future “asbestos”
that will do great harm? We need to be concerned about the potential toxicity of nano-
materials because they are novel and poorly studied. Moreover, nanomaterials have been
observed in unexpected places, e.g., in mitochondria or even in the nucleus. When NPs
become intracellular, they sometimes enter by non-endocytic pathways and appear not
membrane-bound. It is also true that because of their small size, there are greater num-
bers of particles and greater surface area per unit weight than larger respirable particles.
Increasing evidence suggests that toxicity is better correlated with particle number or
surface area than total mass, yet exposures are typically given in terms of mass per unit
volume. In toto, NPs may have unexpected biologic consequences.
It is somewhat reassuring that there are no current examples of nanodiseases in humans.
We know of no epidemic of diseases or conditions elicited by NP exposures. Moreover, the
most exotic and unusual NPs, such as fullerenes and quantum dots, are produced in small
quantities, and exposures of workers or the public are limited. Finally, since dissolution
of particles is proportional to surface area, one would expect that NPs would dissolve
faster than their larger brothers. An exception are carbon nanotubes. They have raised
concerns because they can be similar in size, shape, and durability to asbestos. They also
can translocate in ways reminiscent to asbestos. At high doses in animals, lesions similar
to mesothelioma have been reported.
In conclusion, there are legitimate concerns about nanosafety given the widespread
and increasing use of novel nanomaterials. Data and risk analysis are needed. We need to
discover the laws of nanotoxicology. We should not and cannot evaluate just one material
at a time. It is also important to compare the risks of NPs to other health hazards from
inhaled particles, such as fossil fuel combustion, tobacco, and diverse occupational expo-
sures. Like other new technologies and materials, nanotechnology has great potential
benefits. We need to quantify both benefits and risks in order to make informed and ratio-
nal decisions as individuals and societies.
Readers of this book will be treated to a diverse and delicious menu of new ideas and
data. Inevitably, in addition to providing important answers, new questions are raised.
Readers from many disciplines will find this book valuable. I express my appreciation
to the book editors, who also authored many chapters, Professors Akira Tsuda and Peter
Gehr. They had the vision and persistence to bring this ambitious project to a successful
conclusion.
Joseph D. Brain, SD