Nanomaterials for Medical Applications

467 Pages·2012·7.66 MB·English

by  Zoraida Aguilar (Eds.)

Nanomaterials for
Medical Applications
Zoraida P. Aguilar
Director of Research and Development
Ocean NanoTech
Springdale, AR
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British Library Cataloguing in Publication Data
A catalogue record for this book is available from the British Library
Library of Congress Cataloging-in-Publication Data
Aguilar, Zoraida.
Nanomaterials for medical applications / Zoraida Aguilar.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-12-385089-8
I. Title.
[DNLM: 1. Nanostructures--diagnostic use. 2. Nanostructures--therapeutic use.
3. Biocompatible Materials--chemical synthesis. 4. Biosensing Techniques. QT 36.5]
610.28′4--dc23
2012028617
ISBN: 978-0-12-385089-8
For information on all Elsevier publications
visit our web site at store.elsevier.com
Printed and bound in the USA
12 13 14 15 16 10 9 8 7 6 5 4 3 2 1
Foreword
The encompassing contents and approach of this book on the medical applica-
tions of nanomaterials are unique. Reviewing the various contents of this book,
it is apparent that the primary intent is to provide a reference to people in all
walks of life especially scientists, engineers, medical professionals, law makers,
patent lawyers, students, and common people to inspire new innovations. The
author, Dr Zoraida P. Aguilar, PhD, has put together her experiences in biotech-
nology, nanotechnology, devices, molecular biology, and medical sensors and
devices to describe the current status of nanomaterials for medical applications
and to move existing applications toward the realization of the great potential of
nanoscale science and technology in medicine. She has described nanomaterials
in medicine all the way from their synthesis to the eventual enormous health and
economic impact they will have worldwide. The author ingeniously intercon-
nected the various aspects of an emerging technology and detailed its properties
all the way to the existing and future commercial products.
While nanotechnology has wide and far-reaching applications in vari-
ous industries, its relevance in medicine is beyond doubt. This is because the
nanoscale phenomena is not only applicable to nanomaterials in nanotechnol-
ogy but more so to enzyme action, cell cycle, cell signaling, cell damage, cell
repair, and the metabolic products within the living system. Nanomaterials have
structural features and properties in between those of single atoms/molecules
and continuous bulk materials just like the various biomolecules in the human
body. The only difference is that the nanoscale dimensions of nanomaterials
enable unique optical, electronic, magnetic, and catalytic properties that are
distinct from those of atoms/molecules or bulk/macroscale materials. Proper
control of the growth, size, shape, size/shape distribution, as well as the encom-
passing ligand technologies of these nanomaterials will allow the full exploita-
tion of their unique nanoscale properties enabling the creation of new products,
devices and technologies as well as the improvement of existing ones.
The author successfully presents the most current levels of nanomaterials in
medical research, commercialized products, as well as products in clinical tri-
als. She describes nano-enabled medical products that have entered the market
to date as well as potential applications in complicated diseases such as cancer,
cardiovascular, neurodegenerative disorders, infection, tissue engineering, and
as components of medical implants. Her presentation of the market trends and
the patent landscape provide an overview of commercial and intellectual status
of nanomaterials today.
Aside from the various medical uses of nanomaterials, the author has also
given attention to their potential harmful effects. With any new material, it is
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xii Foreword
necessary to fully understand the potential toxic effects it may have, especially
nanomaterials since their size and bio-accessibility leads to the potential for
quick incorporation into organisms. The author’s presentation of nanotoxicol-
ogy shows a clear balance between the possible advantageous aspects of nano-
materials versus their potential harmful effects to humans. This book’s views on
Nanotoxicology address the toxicity profiles of nanomaterials which are known
to differ from their bulk/larger forms; this has led to the creation and drafting of
various government guidelines worldwide.
As in any new and emerging technology, the current state of intellectual prop-
erty related to nanotechnology is growing tremendously. The author presents a
section on current patent status that is vital for the attaining of its promising
potential beyond academic research. The author has very ingenuously touched
on all the important aspects of nanomaterials to realize their far-reaching appli-
cations in medicine. NO other book in the market has covered such a wide scope
in its presentation of the medical applications of nanomaterials.
Signed:
David P. Battaglia, PhD
PhD in Physical Chemistry with a focus in Nanoscale Materials Science
Preface
Nanotechnology, the 21st century’s cutting edge technology, seeks to discover,
describe, and manipulate the unique properties of matter at the nanoscale to
develop new capabilities with potential applications across all fields of science,
engineering, technology, and medicine. Various potential applications of nano-
materials and nanotechnology have been touted in scientific and layman press
for the promises of the ability of nanoscale technology to revolutionize life into
a fiction that once was found only in books. Outside of enormous speculations
and hype, current applications of nanomaterials and nanodevices that already
impact global commerce are living proofs of the nanotechology revolution.
From its beginning since the late 20th century to its current status in the early
21st century, nanotechnology is continuing to show that it is an evolving tech-
nology that has influenced various areas of research and industry. It has shown
its pivotal and encompassing role and impact on nearly all-industrial sectors. At
the same time, nanotechnology and biotechnology have converged giving rise to
various prospective biomedical applications. Moreover, unlike any other exist-
ing technology, the nanoscale nature of nanomaterials and nanodevices exhibits
potential applications in the sub-cellular scales with near perfect accuracy in
targeting cellular and tissue-specific clinical applications with maximum thera-
peutic effects and with minimal or no bad effects.
During the past decade, increase in awareness and understanding of the
factors that govern growth and properties of nanomaterials gave rise to novel
structures and functionalities that showed applications in electronic indus-
try, biomedical field, computer information technology, and other fields. This
brought a downpour of financial support from various governments worldwide.
Projections of trillions of dollars’ worth of growth in the global nanotechnology
market have led to a scenario guided by competition among the leading players
lead by the US. There are currently a handful (in the hundreds) of nanomateri-
als that have reached commercial productions and applications. These include
those that are used in medicine in the form of drug nanocarriers, imaging con-
trast agents, implants, and other applications. These nano-enabled products
show advantages over their conventional counterparts.
Many more nanomaterials are currently being tested for various sensitive
and accurate medical diagnostics as well as for effective therapeutics. Nano-
materials have become very attractive for drug delivery purposes due to their
unique capabilities and their negligible side effects in cancer therapy and in
the treatment of other ailments. While some nanomaterials are fast advancing
in their medical applications such as chitosan, liposomes, and polymers, a few
others are trailing behind. However, a few of the inorganic nanoparticles have
xiii
xiv   Preface
also advanced faster than others such as the gold, iron oxide, hydroxyapatite,
and gadolinium nanoparticles.
Various instruments that are useful for NMs characterization were discussed.
For clearer and better understanding of nanomaterials and their interactions with
biological systems for medical applications, novel high-resolution imaging and
analysis tools which allow for easy sample preparation and in situ monitoring
are needed. These instruments are also relevant in the desire to regulate and
monitor exposure levels or environmental release of nanomaterials.
It is important to emphasize the role of NMs for drug delivery in cancer,
tumor, and other types of diseases because of the enormous negative impact of
chemotherapy for these diseases. Engineered nanomaterials have the potential
to deliver the chemotherapeutic drugs at the site of the disease to optimize the
effect of drugs while reducing toxic side effects which damage healthy cells.
Nanomaterials can effectively deliver drugs to the tumor bearing organ but these
have to be carefully and meticulously engineered before they can perform the
functions they are designed for. Proper engineering of the nanomaterials must
bring about a desired size, biocompatibility, biodegradability, and must avoid
opsonization for prolonged circulation time so that the drug payload can be
released over an extended period of time. The ability of nano-enabled drugs
that are currently available in the market to minimize the side effects that are
normally observed in conventional drugs open up doors for safer alternatives to
drug delivery.
Just like any new technology or new drug that are intended for human con-
sumption, nanomaterials for medical applications needs scrutiny in terms of
biodistribution, organ accumulation, degradation and/or toxicity, damage of cel-
lular structures or inflammatory effects, and genetic damage. Although the use
of nanomaterials in medicine is still its infancy, studies on absorption, distribu-
tion, metabolism and elimination (ADME), and drug metabolism and pharma-
cokinetics (DMPK) require intense studies. The pharmacokinetics of various
NMs used as drug delivery systems demand exhaustive research including the
path that the nano-enabled drugs take after entry into the living system. One
advantage of a few of the NMs is that they have unique optical and magnetic
properties that may be used while elucidating the ADME and PK in nanodrug
delivery systems.
Thus, as suggested by Richard Feynman at an American Physical Society
meeting at Caltech on December 29, 1959 where he focused on a process which
involved the ability to manipulate down to the individual atoms and molecules
using a set of precise tools to build and operate another proportionally smaller
set is now beginning to come to reality. It was in the early 2000s that the use
of nanotechnology in commercial products began. To date concerted efforts
between academia, government, and industry ascertain the development and
discovery of many new materials with novel properties and new applications.
Various approaches in nanofabrication and nanomaterials synthesis are continu-
ing to grow with the goal of developing more efficient, less expensive, and more
Preface xv
reproducible large scale manufacturing techniques. More sophisticated instru-
mentation for the characterization, detection, and quantification of various NMs
will provide the needed level of analysis to reach molecular and sub-molecular
level applications. It is no longer fiction in nature but a reality that new and
improved biocompatible NMs and nanomechanical components are now being
tested for implants, artificial organs, and greatly improved mechanical, visual,
auditory, and other prosthetic devices. With continued support for research and
development efforts from the various sectors, this may be closer to reality than
we can imagine at this point in time.
The author offers this book as a guide to various important aspects of nano-
materials in order to hasten the realization of its far-reaching applications in
medicine. No other book in the market has covered such a wide scope in its
presentation and approach on the medical applications of nanomaterials.
Acknowledgements
First and foremost I thank God for allowing me to have the knowledge and
courage to undertake a huge project such as this book. Without my faith, the
demise of my beloved mother, the car accident, and the many challenges that
I had to overcome while working on this book, I would have given up and quit
writing. However, I persevered and pushed my limits and with the help of my
family and friends, this book has finally seen the press and now you are about
to read it.
My deepest gratitude goes next to my mom and dad who pushed me into
the field of chemistry. I would not have been what I am now had I pursued my
choice then, which was a career in fine arts. Today, I paint on canvass during my
few leisure moments.
Endless thanks to my mentors, Dr. Paul, Dr. William R. Heineman, and
Dr. Ingrid Fritsch who guided me towards my current maturity in the sciences.
They took time out of their daily busy schedules to provide nurturing academic
advice that paved the way for my path in my professional career especially in
my writing skills.
Sincere thanks goes to Dr. Coy Batoy, Dr. David Battaglia, and Dr. Ruben
Morawicki. You all who have always been there when I needed someone no
matter for what reason, someone to brainstorm with, and someone to hold on to.
Coy is the sweetest darling who searched and provided me with the references
that I could not acquire. Ruben took me out to dinner or a drink when I was too
physically and mentally exhausted and I needed a break. David picked up the
phone whenever I needed someone to hear me on the other line and his wife
Tara, was there to listen to me too. These are friends and professional soul mates
that gave me all the support and encouragement I needed at any time.
Thanks are owed to Dr. Hong Xu, Dr. Hengyi Xu, and Dr. Nick Wu. They
supported me in writing this book with photos, references, and their papers.
Although located in different parts of the country and the world, they were but
one email and one phone call away at all times. Without question or hesitation,
they gave me their wholehearted support and provided what I needed.
Special thanks go to Dr. Susan Grisham Banerjee. She spent hours discuss-
ing various aspects of nanomaterials and their medical and toxicity applications
which are her areas of interest.
There are more people to thank and they are at Ocean NanoTech. Dr. Andrew
Wang, the president of the company provided an all-out support when he learned
that I accepted the challenge to write this book. He offered anything and every-
thing that I needed from Ocean NanoTech. The Vice president of the company,
Alice Bu provided the photos and the catalog which contained the various
xvii
xviii Acknowledgements
products of the company. Just like Andrew, Alice fully supported this book as if
it was one of Ocean’s products. John Dixon, the production scientist provided
me with all the TEM of the various nanomaterials and other photos that he had
on his file so that I may be able to choose the best ones to use. Toni Mohrhauser
provided the disk for the photos and packed the nanomaterials that I needed
when I took some photographs for my on-going projects and for this book. Jenny
Alarcon took a load of photographs especially for the purpose of use in this
book. And Dr. Hong Xu provided the gel electrophoresis photos and fluorescent
microscope images that I used.
My appreciation goes to my son, Ysmael Aguilar, and my niece Christna
Aguilar, who were thrilled that I was writing this book. They sometimes cooked
dinner when I was too engrossed to take a bite. My brother Tony Boy who
provided me advice and encouragement after my mom passed away, my sister
Tess with her constant and continued text messages, and my sister Lyn with her
loving facebook messages.
Many others contributed their heart and soul for me to complete this book.
These are all my friends who are too many to mention but Dr. Marites Sales
deserves a special mention, Mr Albert Morales who has provided me with
encouraging words, Mrs. Edna Pacia Pestano who is the picture of a genuine
altruist, Ms Mayett Maling Cope whose words of wisdom are a daily inspiration,
Mrs Marilou Ramos Szabo whose faith is endless, Mrs Jeneva Canlas Takasawa
who never forgets to call me when I do, my uncle Dr. Vianmar Pascual who does
not forget to send text messages, and my brother Freddie Aguilar with his big
brother words of advice.
To all of you, my sincerest gratitude from the deepest recesses of my soul
for all the support that you have provided me. I hope you all will still be there
for me even after I publish this book. To my publisher, Graham Nisbet and to
Louisa Hutchins, thank you for giving me the opportunity to write and publish
this book.
Very sincerely,
Zoraida P. Aguilar, PhD
Chapter 1
Introduction
Chapter Outline
1.1 Nanotechnology Potential 1.3 Historical and future
Applications and Market perspective 13
Analysis 1 1.4 The future of
1.2 NMs for medical applications 3 nanotechnology 16
This chapter serves as an introduction to nanotechnology and focuses on nanoma-
terials (NMs) in particular. It will introduce the various potential applications of
nanotechnology in general and the various medical applications of NMs in par-
ticular. The chapter will also present a market analysis of nanotechnology and will
converge into the market analysis of NMs specifically in medical applications.
A summary of the various chapters of the book will be presented individually to
have a glimpse of the contents of each chapter. In addition, this chapter will focus
on the market analysis of nanotechnology and of NMs as well as the regulatory
status and the historical perspectives. The author’s view of the future of nanotech-
nology in medicine will be described.
1.1 NANOTECHNOLOGY POTENTIAL APPLICATIONS
AND MARKET ANALYSIS
Nanotechnology seeks to discover, describe, and manipulate the unique proper-
ties of matter at the nanoscale in order to develop new capabilities with potential
applications across all fields of science, engineering, technology, and medicine.
In the United States, the National Nanotechnology Initiative (NNI) was estab-
lished to support the advances in nanoscale science and technology that are
predicted to have an enormous potential economic impact. Various potential
applications of NMs and nanotechnology have been touted in scientific and lay-
man press for the promises of the ability of nanoscale technology to revolution-
ize life as we know it. Outside enormous speculations and hype, the NNI can
point to current applications of NMs and nanodevices that are already impacting
our nation’s commerce as well as advances that are mature enough to promise
impacts in the near future.
Nanomaterials for Medical Applications. http://dx.doi.org/10.1016/B978-0-12-385089-8.00001-7
Copyright © 2013 Elsevier Inc. All rights reserved. 1