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BIOCONJUGATION OF SOFT NANOMATERIALS 91
CHAPTER 5
Nanotechnology and Drug Delivery
XIAOJUN YU, CHANDRA M. VALMIKINATHAN, AMANDA ROGERS,
and JUNPING WANG
5.1 INTRODUCTION
With the advent of science and technology, the ability to understand biology
and medicine has improved tremendously. As almost all biological components
or entities have structures that originate at the submicron level, understanding
and modifications at this level could effect the final performance of such
systems. The simple word ‘‘nano’’ has changed the way that people look at the
environment around them. Nanotechnology is a multidisciplinary scientific
field that applies engineering and manufacturing principles to the design,
synthesis, characterization, and application of materials and devices on
nanoscale [1, 2].
In the last several decades, nanotechnology has been developed in several
areas, which include drug delivery, bioMEMS, tissue engineering, biosensors,
miocrofludics, microarrays, and bioimaging [3]. The nanotechnology-based
drug delivery system has emerged to be the mainstream research among all the
applications because it offers an extraordinary opportunity to make significant
advances in medical diagnosis and treatment. Corporate investment on
nanotechnology for drug delivery and medical diagnostics is increasing year
by year and nanotechnology-based drug delivery has already been commercia-
lized by a lot of companies.
Nanotechnology-based drug delivery is generating continuing interest among
researchers at the federal government agencies as well as private industrial
sectors. According to statistics published in 2002 [1], several foundations and
government agencies like NIH, NSF, and NASA have increased funding new
research ideas and interests in the field of nanotechnology-based drug delivery
systems for targeted and controlled release of therapeutic elements. The field of
BiomedicalNanostructures, EditedbyKennethE.Gonsalves,CraigR.Halberstadt,CatoT.Laurencin,
and Lakshmi S. Nair
Copyright # 2008 John Wiley & Sons, Inc.
93
nanotechnology-based drug delivery system that started as a small division in
2001 by National Nanotechnology Initiative with funding of $116 million is
expected to reach $82 billion by the end of 2007 [4] and is expected to grow
stronger and attract further investments [5]. On the industrial side, pharma-
ceutical companies have started to invest into projects that modify existent
delivery systems. The demand for drug delivery systems in the United States has
grown rapidly and bounds to create a niche for itself in the market for
innovative technologies that will change the face of science and technology.
There are around 150 companies that have active research divisions working on
targeted controlled drug delivery and this number is bound to increase in the
near future owing to tremendous developments in the field of medicine and
increased understanding of the human anatomy and diseases associated with
it [6].
Traditional nanotechnology for drug delivery mainly referred to those
nanoscale vehicles which were mainly utilized to improve the drug bioavail-
ability and minimize the side effects of the drug by holding or transporting the
drug molecules to the desired locations. Recently, new nanoscale platforms
have been under development for not only therapeutic purpose but also
diagnostic applications [7]. In addition to the traditional function of drug
delivery, these nanotools have been utilized for medical diagnostics via
fluorescent imaging [8] or magnetic resonance imaging (MRI) [9], as well as for
some new therapeutic strategies such as the photothermal therapeutics in
clinical oncology [10]. Investigations on multifunctional nanoparticles with the
combination of therapeutic, targeting, and imaging functions for advanced
drug delivery systems have drawn more and more attention from current
researchers [11–13].
5.2 ADVANTAGES OF NANOSTRUCTURED DELIVERY SYSTEMS
Once a stable and effective active pharmaceutical ingredient (API) has been
identified, there are several ways to administer it into the human body. The most
common ways of administration are oral, transdermal, and nasal delivery methods
[14]. The oral delivery pathway is the easiest and most sought-after delivery
method but has its own disadvantages with the current designs. The limitations
include reduced bioavailability and ineffective way to deliver proteins and peptides
due to the effects of pH in the digestive system, the effect of passage through
various organs, and the effects of stress from the intestines [15]. The nasal and
transdermal methods cause patient discomfort and also have reduced efficiency
and availability in the system [16]. Other challenges involved in conventional drug
delivery systems include difficulties for providing reproducible amounts of release
per fixed time frame, poor solubility of drugs, and difficulties for targeting specific
regions without affecting healthy tissues [6]. Nanotechnology-based drug delivery
systems have many advantages and provide the insight for solving the problems
associated with conventional drug delivery systems.
94 BIOMEDICAL NANOSTRUCTURES
5.2.1 Localized and Targeted Delivery
Nanotechnology-base d drug delivery systems can be controlled to deliver drugs
to specific sites and target drugs to certain cells only, withou t affecting
neighboring normal cells [17, 18]. Several external stimuli such as ultrasound
and magnetic field have been able to influence drug targeting in nanocarriers
for tumor eradication. Several biologically relevant molecules such as
transferrin [19], folate [20], and antibodies [21] play important roles in internal
targeting and internalization of drugs. The localized and targeted delivery
greatly helps in reducing systemic toxicity and largely increases effectiveness of
the therapeutic ingredients [6].
5.2.2 Controlled Delivery
The nanotechnology-based drug delivery platform provides researchers with
options to deliver highly toxic drug intermediates and complexes, as well as
DNA and viral vectors at optimum dosages at controlled intervals of time [16].
Release profile from materials largely depends upon the nature of the delivery
system. By choosing the correct type of materials for preparation of nan-
oparticles, the release profile can be modified [22]. In addition, nanotechnology
opens the door to modify the property of materials at the atomic scale leading
to creation of materials with varied delivery rates that are extremely
controllable [23].
5.2.3 Enhanced Circulation Time and Biodistribution
Nanocarriers may increase the circulation time of drugs within the body.
Particle size is intrinsically related to rate of clearance from the circulation.
Larger particles tend to be removed much faster than smaller particles. In
addition to increased circulation time, nanoparticles also exhibit enhanced
biodistribution over their larger counterparts. When administered to test
animals, larger particles tend to be found in high concentrations in the spleen
and liver rather than in the target locations. Smaller particles are more likely to
be taken up by other cells within the body, including target cells [24].
5.2.4 Drug Solubility
Nanotechnology allows for the delivery of all types of drugs. Particularly, it
has been especially effective for the delivery of drugs exhibiting poor solubility
in water to living tissues. Micelles, which are typically assembled from
amphiphilic materials, possess a hydrophobic core surrounded by a hydrophilic
outer layer , known as a corona. Hydrophobic molecules may be easily
encapsulated in the microenvironment of the core. The hydrophilic corona
facilitates travel of the nanoparticles through water-based solutions. This
NANOTECHNOLOGY AND DRUG DELIVERY 95