Nanotechnology ("nanotech") is the manipulation of matter on an atomic, molecular, and supramolecular scale.

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1. Introduction
A growing interest in the medical applications of nanotechnology has led to the emergence of a
new field called nanomedicine (Saha, 2009). Nanomedicine offers the prospect of powerful new
tools for the treatment of human diseases and the improvement of human biological systems
using molecular nanotechnology. Nanotechnology, ‘the manufacturing technology of the 21st
century’, will provide an opportunity to build a broad range of economically complex molecular
machines (including, not incidentally, molecular computers). It will lead to the building of
computer controlled molecular tools much smaller than a human cell with the accuracy and
precision of drug molecules. Such tools will allow medicine, for the first time to intervene in a
sophisticated and controlled way at the cellular and molecular level (Ralph, 1996). They could
remove obstructions in the circulatory system, kill cancer cells, or take over the function of sub
cellular organelles. Just as today the artificial heart has been developed, so in the future, perhaps
artificial mitochondrion would be developed (Ralph, 1996).
The ultimate goal of nano medicine is to improve the quality of life. Broadly the aim of nano
medicine may is the comprehensive monitoring, repairing and improvement of all human
biological systems, working from the molecular level using engineered devices and
nanostructures to achieve medical benefit. Taken together, nanomedicine is the process of
diagnosing, treating, and preventing disease and traumatic injury, relieving pain, and of
preserving and improving human health, using molecular tools and molecular knowledge of the
human body (Freitas, 2002).
However, nano materials are now being designed to aid the transport of diagnostic or therapeutic
agents through biologic barriers; to gain access to molecules; to mediate molecular interactions;
and to detect molecular changes in a sensitive, high through put manner. In contrast to atoms and
macroscopic materials, nano materials have a high ratio of surface area to volume as well as
tunable optical, electronic, magnetic, and biologic properties, and they can be engineered to have
different sizes, shapes, chemical compositions, surface chemical characteristics, and hollow or
solid structures (Xia et al., 2009; Peer et al., 2007).

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2. Defination
2.1. Defination of Nanotechnology
Nanotechnology is the development and use of techniques to study physical phenomena and
construct structures in the physical size range of 1-100 nanometers (nm), as well as the
incorporation of these structures into applications ( Kostoff et al., 2007).
It can be defined as the “intentional design, characterization, production,and applications of
materials, structures, devices, and systems by controlling their size and shape in the nanoscale
range (1 to 100 nm).” (Kim et al., 2010). In other sense it can simply be defined as the
technology at the scale of one-billionth of a metre. It is the design, characterization, synthesis
and application of materials, structures, devices and systems by controlling shape and size at
nanometer scale (Stylios et al., 2005). It is the ability to work at the atomic, molecular and
supramolecular levels to create and employ materials, structures, devices and systems with
basically new properties (Roco, 2003). Scientifically, nanotechnology is employed to describe
materials, devices and systems with structures and components exhibiting new and significantly
improved physical, chemical and biological propertiesas well as the phenomena and processes
enabled by the ability to control properties at nanoscale (Miyazaki and Islam, 2007).
Materials exhibit unique properties at nanoscale of 1 to 100 nanometre (nm). The changes in
properties are due to increase in surface area and dominance of quantumeffects which is
associated with very small sizes and large surface area to volume ratio (Williams, 2008). The
quantum effects at nanoscale determine a material’s magnetic, thermal, optical and electrical
properties. It is expected generally,that products at nanoscale will be cheaper due to less quantity
of materials utilized.
2.2. Defination of Nanomedicine
Nanomedicine is the application of nano technology to medicine. It is the preservation and
improvement of human health, using molecular tools and molecular knowledge of the human

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body. Present day nanomedicine exploits carefully structured nanoparticles such as dendrimer,
carbon fullerenes and nanoshells (Mashino T et al., 2005) to target specific tissue and organs.
These nanoparticles may serve as diagnostic and therapeutic antiviral, antitumor or anti cancer
agents. But as this technology mature in the year ahead, complex nanodevices and even
nanorobots will be farbricated, first of biological material but later using more durable materials
such as diamond to achieve the most powerful result. (Freitas jr RA, 2000)
3. Application in medicine and health care /Diseases and Cures by Nanomedicine
Medical science has scored some impressive successes. Antibiotics have reduced diseases caused
by bacteria remarkably. Nowadays, vitamin and mineral deficiency diseases are rare in
developed nations. However, there are still many diseases that limit our lifespan, and the
medicines concerned can only postpone them but are not able to cure. Life cannot be extended
indefinitely without curing each disease that threatens to shorten it.
The application of nanotechnology to the medical sector is referred to as Nanomedicine.
Specifically, this area of application uses nanometre scale materials and nano-eneabled
techniques to diagnosis, monitor, treat and prevent diseases. These include cardiovascular
diseases, cancer, musculoskeletal and inflammatory conditions, neurodegenerative and
psychiatric diseases, diabetes and infectious diseases (bacterial and viral infections, such as
HIV). The potential contribution of nanotechnology in the medical sector is extremely broad and
includes new diagnostic tools, imaging agents and methods, drug delivery systems and
pharmaceuticals, therapies, implants and tissue engineered constructs (Kubik et al., 2005).

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Table 1: Application of Nanomedicine for the Healthcare (Bharali et al., 2009; Park, 2002;
Thorek et al., 2006; Partha and Conyers, 2009; Stya and Srinivasa, 2006; Hirsch et al., 2006)
3.1 Treatment of Cancer
Today’s monoclonal antibodies are able to bind to only a single type of protein or other antigen,
and not proved effective against most cancers. The cancer-killing device mentioned here could
incorporate a dozen different binding sites and so could monitor the concentrations of a dozen
different types of molecules. The computer could determine if the profile of concentrations fit a
pre-programmed “cancerous” profile and would, when a cancerous profile was encountered,
release the poison (Ralph, 1996; Saha, 2009)

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3.2 Prevention of Brain Damage in Neurodegenerative Diseases
Damaged neurons, like other cells, sometimes go into suicide mode (called “apoptosis”); this can
be chemically prevented, and the neuron can be stabilized until the problem is fixed and the
damage is repaired. It is now acknowledged that brain cells do regenerate; the brain is generating
new cells all the time. This implies that some neural death is normal. It seems that a new neuron
can take its cues from the existing ones; this means that a person’s mind may be intact even after
the death and replacement of a large percentage of their neurons. Finally, it may be possible to
measure neural connections and/or activity in enough detail to simulate the firing pattern. This
may make it possible to create an artificial neuron or even an artificial neural net that can be used
to replace missing neurons and retain old memories. But even if this proves to be impossible, the
worst-case scenario is one in which people cannot remember much farther than a century back.
More memory loss than this can be accepted as a natural consequence of aging (Saha, 2009)
3.3 Hormone Deficiency
Aging is associated with changes in the levels of many hormones; perhaps the best known
example is menopause, which is caused by a reduction in estrogen. It is likely that treating glands
against aging at the cellular level would restore age-appropriate hormone production. However,
if this is not enough to bring the body to a younger state, artificial glands could be built that
would maintain the desired hormone levels. In fact, different hormone levels could be supplied to
different organs -something that the body cannot do for itself. This would be an example of
heterostasis (Saha, 2009).
3.4 For the treatment of Infection
With great effort, we managed to eradicate smallpox using 1970’s technology. Cheap
manufacturing would allow the creation of billions of doses of highly effective treatments that
would be easy to distribute and administer; the main obstacles to wiping out many diseases
worldwide would be political, not economic or technological. Nanorobotic ‘Microbivores’ the

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nanorobotic phagocytes (artificial white cells) traveling in the bloodstream could be 1000 times
faster-acting than white blood cells and eradicate 1000 times more bacteria, offering a complete
antimicrobial therapy without increasing the risk of sepsis or septic shock (as in traditional
antibiotic regimens) and without the release of biologically active effluents. Microbivores could
also be useful for treating infections of the meninges or the cerebrospinal fluid (CSF) and
respiratory diseases involving the presence of bacteria in the lungs or sputum, and could also
digest bacterial biofilms. These handy nanorobots could quickly rid the blood of nonbacterial
pathogens such as viruses (viremia), fungus cells (fungemia), or parasites (parasitemia). Outside
the body, microbivore derivatives could help clean up biohazards, toxic biochemicals or other
environmental organic materials spills, as in bioremediation (Saha, 2009).
3.5 For Life Saving after Accidents
Primary medical applications of respirocytes would include transfusable blood substitution;
partial treatment for anemia, perinatal/neonatal, and lung disorders; enhancement of
cardiovascular/neurovascular procedures, tumor therapies and diagnostics; prevention of
asphyxia; artificial breathing; and a variety of sports, veterinary, battlefield, and other uses. The
clottocytes are artificial platelets that could stop human bleeding within ~1 second of physical
injury, but using only 0.01% the bloodstream concentration of natural platelets. In other words,
nanorobotic clottocytes would be around 10,000 times more effective as clotting agents than an
equal volume of natural platelets. Nanorobotic artificial mechanical platelets (Clottocytes) could
allow for complete hemostasis in as little as one second - 100 to 1000 times faster than the
natural system. They could also work internally. Using acoustic pulses, a blood vessel break
could be rapidly communicated to neighboring clottocytes, immediately triggering a progressive
controlled mesh-release cascade (Freitas, 1998).

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3.6 Diagnostic Imaging
Techniques such as X-ray, computer tomography (CT), ultrasound (US), magnetic resonance
imaging (MRI) and nuclear medicine (NM) are well established imaging techniques, widely used
both in medicine and biochemical research. Originally, imaging techniques could only detect
changes in the appearance of a tissue when the symptoms of the disease were relatively
advanced. Later, targeting and contrast agents were introduced to mark the disease site at the
tissue level, increasing imaging specificity and resolution. It is in this specific area that
nanotechnology is making its highest contribution by developing better contrast agents for nearly
all imaging techniques. The physiochemical characteristics of the nanoparticles (particle size,
surface charge, surface coating and stability) allow the redirection and the concentration of the
marker at the site of interest. An example of nanoparticles used in research for imaging are
perfluorocarbon nanoparticles employed as contrast agents for nuclear imaging, magnetic
resonance imaging and ultrasound, with application to the imaging of blood clots, angiogenesis,
cancer metastases and other pathogenic changes in blood vessels. Gadolium complexes have
been incorporated into emulsion nanoparticles for the molecular imaging of thrombus resulting
in a dramatic enhancement of the signal compared to usual MRI contrast agents (Flacke et al.,
2001).
Figure 1. Low-resolution images (3D GraSE) of fibrin clots targeted with nanoparticles
presenting a homogeneous, T1-weighted enhancement that improves with increasing gadolinium
level (0, 2.5, and 20 mol%). (Flacke et al., 2001).

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4. Nanotechnology and medical applications:
4.1 Liposomes
Liposomes were first developed about 40 years ago. They are small artificial vesicles(50 –
100nm) developed from phospholipids such as phosphatidylcholine,
phosphatidylglycerol,phosphatidylethanolamine and phosphatidylserine, which have been used
in biology, biochemistry, medicine, food and cosmetics( Shafirovich et al., 2007; Patel-Predd ,
2008;Hu et al., 2003;Heron et al., 2007).The characteristics of liposomes are determined by the
choice of lipid, their composition, method of preparation, size and surface charge(Stylios et al.,
2005). Liposomes have been applied as drug carriers due to their ability to prevent degradation
of drugs, reduce side effects and target drugs to site of action (Cortie, 2004). However,limitations
of liposomes include low encapsulation efficiency, rapid leakage of water-soluble drug in the
presence of blood components and poor storage stability (Cortie , 2004;Cortie and van der
Lingen , 2002). However, surface modification may confer stability and structure integrity
against harsh bio-environment after oral or parenteral administration (Overbury, 2005). Surface
modification can be achieved by attaching polymers such as poly (methacrylic acid-co-stearyl
methacrylate) and polyethylene glycol units to improve the circulation time of liposomes in the
blood; and by conjugation to antibodies or ligands such as lectins for target specific drug
delivery and stability (Cortie and van der Lingen , 2002; Overbury , 2005; Jain et al., 2008).
Applications of liposomes include transdermal drug delivery to enhance skin permeation of
drugs with high molecular weight and poor water solubility (Roco , 1999); a carrier for delivery
of drugs, such as gentamicin, in order to reduce toxicity( Yin , 2007); possible drug delivery to
the lungs by nebulisation(Eijkel and van den Berg , 2006); ocular drug delivery ( Sheeparamatti
et al.,2007) and in the treatment of parasitic infections. However, solid lipid nanoparticles
(SLNs) provide an effective alternative due to their stability, ease of scalability and
commercialisability (Smith, 2006).

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Other vesicular structures include transferosomes, ethosomes, niosomes and marinosomes which
are used mainly for transdermal delivery (Shafirovich et al., 2007; Ball , 2005;Bittner , 2005).
Figure 2: Liposome for drug delivery (Smith, 2006).
Liposomes discovered in mid 1960s were the original models of nanoscaled drug delivery
devices.They are spherical nanoparticles made of lipid bilayer membranes with an aqueous
interior but can be unilamellar with a single lamella of membrane or multilamellar with multiple
membranes. They can be used as effective drug delivery systems. Cancer chemotherapeutic
drugs and other toxic drugs like amphotericin and hamycin, when used as liposomal drugs
produce much better efficacy and safety as compared to conventional preparations. These
liposomes can be loaded with drugs either in the aqueous compartment or in the lipid membrane.
Usually water soluble drugs are loaded in aqueous compartment and lipid soluble drugs are
incorporated in the liposomal membrane (Gregoriadis and Ryman, 1972). The major limitation
of liposome is its rapid degradation and clearance by the liver macrophages (McCormack and
Gregoriadis, 1994),

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thus reducing the duration of action of the drug it carries. This can be reduced to a certain extent
with the advent of stealth liposomes where the liposomes are coated with materials like
polyoxyethylene (Illum and Davis, 1984) which prevents opsonisation of the liposome and their
uptake by macrophages (Senior et al., 1991). Other ways of prolonging the circulation time of
liposomes are incorporation of substances like cholesterol (Kirby and Gregoriadis, 1983),
polyvinylpyrollidone polyacrylamide lipids (Torchilin et al., 1994) and high transition
temperature phospholipids distearoyl phosphatidylcholine (Forssen et al., 1992).
4.1.1 Targeting of liposomal drugs
Immunoliposomes are liposomes conjugated with an antibody directed towards the tumour
antigen. These immunoliposomes when injected into the body, reaches the target tissue and gets
accumulated in its site of action. This reduces unwanted effects and also increases the drug
delivery to the target tissue, thus enhancing its safety and efficacy (Surendiran et al., 2009).
The targeted liposomal preparations are found to have a better efficacy than non targeted
liposomes.
4.2 Nanopores
Nanopores designed in 1997 by Desai and Ferrari (Desai et al., 1998), consist of wafers with
high density of pores (20 nm in diameter). The pores allow entry of oxygen, glucose and other
products like insulin to pass through. However, it does not allow immunoglobulin and cells to
pass through them. Nanopores can be used as devices to protect transplanted tissues from the
host immune system, at the same time, utilizing the benefit of transplantation. β cells of pancreas
can be enclosed within the nanopore device and implanted in the recipient’s body. This tissue
sample receives the nutrients from the surrounding tissues and at the same time remains
undetected by the immune system and hence do not get rejected. This could serve as a newer
modality of treatment for insulin dependent diabetes mellitus (Leoni and Desai, 2001).

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Nanopores can also be employed in DNA sequencing. Nanopores are also being developed with
ability to differentiate purines from pyrimidines. Further, incorporation of electricity conducting
electrodes is being designed to improve longitudinal resolution for base pair identification (
Freitas , 2005).Such a method could possibly read a thousand bases per second per pore. These
can be used for low cost high throughput genome sequencing (Deamer and Akeson , 2000)which
would be of great benefit for application of pharmacogenomics in drug development process.
4.3 Fullerenes
Fullerenes, a carbon allotrope, also called as “bucky balls” were discovered in 1985 (Thakral and
Mehta, 2006).The buckminster fullerene is the most common form of fullerene measuring about
7 A in diameter with 60 carbon atoms arranged in a shape known as truncated icosahedrons
(Kratschmer et al., 1990). It resembles a soccer ball with 20 hexagons and 12 pentagons and is
highly symmetrical (Taylor et al., 1990).
4.3.1 Types of fullerenes
Alkali doped fullerenes are structures with alkali metal atoms in between fullerenes
Contributing valence electrons to neighbouring fullerenes (Chandrakumar and Ghosh ,
2008).They occur because of the electronegative nature of the fullerenes.
Endohedral fullerenes have another atom enclosed inside the buckyball. If a metallic atom is
enclosed,these are called as metallofullerenes ( Fatouros et al., 2006; Komatsu et al., 2005).
Due to the small size of C60 fullerene, it is difficult to synthesize endohedral C60 fullerenes.
However, larger fullerenes such as C82 or C84 fullerenes are used for synthesizing endohedral
fullerenes. Endohedral metallofullerenes can be used for diagnostic purposes as radio contrast
media in magnetic resonance imaging and other imaging procedures. Since the radioactive metal
is enclosed within the buckyball, these are less toxic and safer. This method can also be
employed for imaging organs as radioactive tracers (Komatsu et al., 2005).

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Exohedral fullerenes also called as fullerene derivatives are synthesized by chemical reaction
between the fullerene and other chemical groups.
These are also called as functionalized fullerenes. Such fullerenes can be used as photosensitizers
in photodynamic therapy for malignancies. These generate reactive oxygen species when
stimulated by light and kills the target cells. This method is now also being investigated for
antimicrobial property as these cause cell membrane disruption especially in Gram positive
bacteria and mycobacterium (Mroz et al., 2007; Tegos et al., 2005; Bosi et al., 2000).
Heterofullerenes are fullerene compounds where one or more carbon atoms are replaced by other
atoms like nitrogen or boron (Thakral and Mehta, 2006).
Fullerenes are being investigated for drug transport of antiviral drugs, antibiotics and anticancer
agents (Mroz et al., 2007; Tegos et al., 2005; Bosi et al., 2000; Ji et al., 2008).
Fullerenes can also be used as free radical scavengers due to presence of high number of
conjugated double bonds in the core structure. These are found to have a protective activity
against mitochondrial injury induced by free radicals (Cai et al., 2008).
However, fullerenes can also generate reactive oxygen species during photosensitization. This
property can be used in cancer therapy (Markovic and Trajkovic, 2008).
Fullerenes have the potential to stimulate host immune response and production of fullerene
specific antibodies. Animal studies with C60 fullerene conjugated with thyroglobulin have
produced a C60 specific immunological response which can be detected by ELISA with IgG
specific antibodies. This can be used to design methods of estimation of fullerene levels in the
body when used for therapeutic or diagnostic purposes (Chen et al., 1998).On intravenous
injection, these get distributed to various parts of the body and get excreted unchanged through
the kidney. Soluble derivates of fullerenes are more biocompatible compared to insoluble forms
of fullerenes and have low toxic potential even at higher doses (Chen et al., 1998). Further, the
degree of purification of fullerene determines its cost and highly purified fullerenes are
expensive, restricting its application in medical field (Thakral and Mehta, 2006).

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4.4 Biosensors
A sensor is a device capable of recognizing a specific chemical species and ‘signalling’ the
presence, activity or concentration of that species in solution through some chemical change. A
‘transducer’ converts the chemical signal (such as a catalytic activity of a specific biomolecule)
into a quantifiable signal (such as a change in colour or intensity) with a defined sensitivity.
When the sensing is based on biomolecular recognition it is called a biosensor. There are various
types of biosensors, such as antibody/antigen based, nucleic acid based and enzyme based. Also,
depending on the technique used in signal transduction, biosensors are classified as optical-
detection biosensors (as in the example above), electrochemical biosensors, mass-sensitive
biosensors and thermal biosensors (Kubik et al., 2005; Vo-Dinh and Cullum, 2000). One
miniaturized biosensor concept makes use of small beams that bend when biological molecules
become captured at the surface inducing a surface stress (see Figure 3).
Figure 3.1 Schematic diagram of a cantilever based biosensor. The yellow molecules bind
specifically to the red molecules on the right hand cantilever and are detected by the bending of
the cantilever (Wang and Branton, 2001).
There are numerous nanoparticles that can be used as biosensors components (Medina et al.,
2007). These work as probes recognizing an analyte or differentiating between analytes of
interest. In such applications some biological molecular species are attached to the surface of the
nanoparticles to recognize, through a key -and-lock mechanism, the target of interest. The probes

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then signal the presence of the target by a change in color, mass or other physical change.
Nanoparticles that are used as elements for biosensors include quantum dots, metallic nanobeads,
silica nanoparticles, magnetic beads, and fullerenes, which are hollow cages of carbon, shaped
like soccer balls.
Other biosensors use nanostructured particles as nano-sieves through which charged molecules
are transported in an electric field. In this case particles with engineered nanopores are used
(Wang and Branton, 2001).
4.5 Nanotubes
Carbon nanotubes discovered in 1991 (Iijima, 1991) are tubular structures like a sheet of graphite
rolled into a cylinder capped at one or both ends by a buckyball. Nanotubes can be single walled
carbon nanotube (SWCNT) or multiwalled carbon nanotube (MWCNT) in concentric fashion.
Single walled nanotube has an internal diameter of 1-2 nm and multiwalled nanotube has a
diameter of 2-25 nm with 0.36 nm distance between layers of MWCNT. These vary in their
length ranging from 1 μm to a few micrometers (Reilly, 2007). These are characterized by
greater strength and stability hence can be used as stable drug carriers. Cell specificity can be
achieved by conjugating antibodies to carbon nanotubes with fluorescent or radiolabelling
(McDevitt et al., 2007). Entry of nanotubes into the cell may be mediated by endocytosis or by
insertion through the cell membrane. Carbon nanotubes can be made more soluble by
incorporation of carboxylic or ammonium groups to their structure and can be used for the
transport of peptides, nucleic acids and other drug molecules. Indium-111 radionuclide labelled
carbon nanotubes are being investigated for killing cancer cells selectively (Reilly, 2007).
Amphotericin B nanotubes has shown increased drug delivery to the interior of cells compared to
amphotericin B administration without nanotubes (Prato et al., 2008). The efficacy of
amphotericin B nanotubes was greater as an antifungal agent compared to amphotericin B alone
and it was effective on strains of fungi which are usually resistant to amphotericin B alone.
Further, there was reduced toxicity to mammalian cells with amphotericin B nanotubes (Prato et
al., 2008).The ability of nanotubes to transport DNA across cell membrane is used in studies

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involving gene therapy. DNA can be attached to the tips of nanotubes or can be incorporated
within the tubes (Prato et al., 2008).showed greater expression of the β galactosidase marker
gene through nanotubes compared to transfer of naked DNA. This confers the advantage of non
immunogenicity in contrast to viral vectors used for gene transfer. Gene silencing studies with
small interfering RNA (siRNA) have been done as a modality of cancer therapy where tumour
cells will be selectively modulated. Functionalized single walled carbon nanotubes can be used
with siRNA to silence targeted gene expression (Zhang et al., 2006).
It was observed that carbon nanotubes, except acetylated ones, when bonded with a peptide
produce a higher immunological response compared to free peptides. This property can be used
in vaccine production to enhance the efficacy of vaccines. Further, it was also found that
compounds bound to nanotubes increase the efficacy of diagnostic methods like ELISA. These
can also be used for designing of biosensors owing to property of functionalization and high
length to diameter aspect ratio which provides a high surface to volume ratio (Pantarotto et al.,
2003; Balasubramanian and Burghard, 2006).
Water insoluble forms of nanotubes like pristine carbon nanotubes have high in vitro toxicity
compared to modified water dispersible forms of nanotubes. It was also seen that the toxic
potential decreases withfunctionalization. Further, functionalization also affects the elimination
of the nanotube. SWCNTs without conjugation to monoclonal antibody have a high renal uptake
and modest liver uptake as compared to SWCNTs with conjugation to monoclonal antibody
having higher liver uptake and lower renal uptake (Reilly, 2007).
Carbon nanotubes and nanowires are also employed for sensing (Kong et al., 2000; Collins et al.,
2000; Cui et al., 2001). The latter can be fabricated out of a semiconductor material and their
size tuned to have a specific conducting property. This, together with the ability to bind specific
analytes on their surface, yields a direct, label-free electrical readout (Cui et al 2001; Patolsky et
al., 2006). These nanowires biosensors allow detecting a wide range of chemical and biological
species, including low concentration of protein and viruses and their application spans from the
medical to the environmental sector. Figure 4 illustrates a silicon nanowires biosensor based on
biorecognition.

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Figure 3.2 Biorecognition on a silicon nanowire biosensor. The surface of the nanowire is
modified with avidin molecules (purple stars) which can selectively bind a streptavidin-
functionalised molecule or nanoparticle (Reilly, 2007).
4.6 Quantum dots
Quantum dots are nanocrystals measuring around 2-10 nm which can be made to fluorescence
when stimulated by light. Their structure consists of an inorganic core, the size of which
determines the colour emitted an inorganic shell and an aqueous organic coating to which
biomolecules are conjugated. The biomolecule conjugation of the quantum dots can be
modulated to target various biomarkers (Iga et al., 2007).
Quantum dots can be used for biomedical purposes as a diagnostic as well as therapeutic tool.
These can be tagged with biomolecules and used as highly sensitive probes. A study done on
prostate cancer developed in nude mice has shown accumulation of quantum dots probe by
enhanced permeability and retention as well as by antibody directed targeting (Gao et al.,
2004).The quantum dots conjugated with polyethylene glycol (PEG) and antibody to prostate
specific membrane antigen (PSMA) were accumulated and retained in the grafted tumour tissue
in the mouse (Gao et al., 2004).
Quantum dots can also be used for imaging of sentinel node in cancer patients for tumour staging
and planning of therapy. This method can be adopted for various malignancies like melanoma,
breast, lung and gastrointestinal tumours (Iga et al., 2007). Quantum dot probes provide real time
imaging of the sentinel node with Near Infra Red (NIR) fluorescence system. The NIR region of

17. 17
the electromagnetic spectrum produces reduced background noise and deeper penetration of rays,
of up to 2 to 5 cm into the biological sample. However, the traditional fluorescence dyes yield
low signal intensity when used in NIR region. This limitation is overcome, by using NIR
fluorescence system with quantum dot probes. The fluorescence produced by quantum dots is
much brighter than those produced by conventional dyes when used with NIR fluorescence
system (Amiot et al., 2008).However, the application of quantum dots in a clinical setting has
limitations owing to its elimination factors. Functionalization of the quantum dots which protects
from the toxic core, leads to increase in size of the nanoparticle greater than the pore size of
endothelium and renal capillaries, thus reducing its elimination and resulting in toxicity. Also, in
vivo studies are lacking on the metabolism and excretion of quantum dots (Iga et al., 2007).
4.7 Nanoshells
Nanoshells were developed by West and Halas (West and Halas, 2000). At Rice University as a
new modality of targeted therapy. Nanoshells consist of nanoparticles with a core of silica and a
coating of thin metallic shell. These can be targeted to desired tissue by using immunological
methods. This technology is being evaluated for cancer therapy. (Hirsh et al., 2003) used
nanoshells which are tuned to absorb infra red rays when exposed from a source outside the body
to demonstrate the thermo ablative property of nanoshells. The nanoshells when exposed to NIR
region of the electromagnetic spectrum get heated and cause destruction of the tissue. This has
been studied in both in vitro and in vivo experiments with HER 2 expressing SK-BR-3 human
breast carcinoma cells. The control cells did not lose their viability even after treatment with
nanoshells with non specific anti IgG or PEG and NIR ablation (Lowery et al., 2006).
Nanoshells can also be embedded in a hydrogel polymer containing the drug. After directing the
nanoshells to the tumour tissue by immunological methods, with an infrared laser, these can be
made to get heated up, melting the polymer and releasing the drug at the tumour tissue. Targeting
the drug release avoids the toxicity of cancer chemotherapy drugs. Nanoshells are currently
being investigated for micro metastasis of tumours and also for treatment of diabetes (Freitas,
2005; Kherlopian., 2008).

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Nanoshells are also useful for diagnostic purposes in whole blood immunoassays. Gold
nanoshells can be coupled to antibodies and the size can be modulated so that it responds to NIR
wavelength, which has the ability to penetrate whole blood specimens. With this method it is
possible to detect immunoglobulins at a concentration range of nanograms per millilitre in
plasma and whole blood (Freitas, 2005).
4.8 Nanobubbles
Cancer therapeutic drugs can be incorporated into nanoscaled bubble like structures called as
nanobubbles. These nanobubbles remain stable at room temperature and when heated to
physiological temperature within the body coalesce to form microbubbles. These have the
advantages of targeting the tumour tissue and delivering the drug selectively under the influence
of ultrasound exposure. This results in increased intracellular uptake of the drug by the tumour
cells. It also provides an additional advantage of enabling visualisation of the tumour by means
of ultrasound methods (Klibanov, 2006; Gao et al., 2008). (Rapaport et al., 2007) have
demonstrated the utility of nanobubbles in delivery of drugs like doxorubicin based on in vitro
and in vivo experiments using breast cancer cells MDA MB231 and mice with breast cancer
xenograft respectively. On administration of nanobubble loaded doxorubicin, these reach the
tumour tissue through leaky vasculature and get accumulated at the site of tumour. This is
followed by formation of microbubbles by coalescing of nanobubbles which can be visualized by
ultrasound techniques. When the site is focused with high intensity focused ultrasound (HIFU), it
causes disruption of the microbubbles resulting in release of the drug. The microbubbles retained
the drug in a stable state until stimulated by HIFU. This results in attainment of higher levels of
drug in the target cells and hence reduced toxicity and increased efficacy. This method needs
further exploration for its utility in treatment of various malignancies. Liposomal nanobubbles
and microbubbles are also being investigated for their role as effective non viral vectors for gene
therapy. Nanobubbles combined with ultrasound exposure has shown improved transfer of gene
in both in vitro and in vivo studies (Negishi et al., 2008; Suzuki et al., 2008). Nanobubbles are
also being tried as a therapeutic measure for removal of clot in vascular system in combination
with ultrasound, a process called as sonothrombolysis. This method has advantages of being non
invasive and causing less damage to endothelium (Iverson et al., 2008).

19. 19
4.9 Paramagnetic nanoparticles
Paramagnetic nanoparticles are being tried for both diagnostic and therapeutic purposes.
Diagnostically, paramagnetic iron oxide nanoparticles are used as contrast agents in magnetic
resonance imaging. These have a greater magnetic susceptibility than conventional contrast
agents. Targeting of these nanoparticles enables identification of specific organs and tissues
(Cuenca et al., 2006).The use of iron oxide in MRI imaging faces limitations like specificity and
internalization by macrophages (Peng et al., 2008). Paramagnetic nanoparticles conjugated with
antibodies to HER-2/neu which are expressed on breast cancer cells have been used with MRI to
detect breast cancer cells in vitro (Artemov et al., 2003).Study done by (Leuschner et al., 2005)
has demonstrated the in vivo detection of breast cancer cells using paramagnetic nanoparticles
conjugated with luteinizing hormone releasing hormone as breast cancer cells express LHRH
receptors. Thus, use of antibodies to direct the nanoparticle to the target site helped to overcome
problems with specificity of action. Internalization of the nanoparticles by macrophages can be
reduced by treatment with drugs like lovastatin which reduce macrophage receptor expression
for the nanoparticle by reducing the recycling of receptors (Peng et al., 2008). Further, injection
of decoys of nanoparticle can be used to eliminate plasma opsonins and reduce uptake of the
nanoparticles. Also, change of surface charge of the nanoparticle to neutral by covalent coupling
to chemicals leads to an increase in circulation time (Peng et al., 2008).
Monocrystalline iron oxide nanoparticles (MIONs) have been studied by (Knauth et al., 2001) in
magnetic resonance imaging of brain. MIONs help in overcoming the disadvantage of surgically
induced contrast enhancement with traditional contrast agents resulting in misinterpretation
during intra-operative MR imaging of brain. Surgically induced contrast enhancement occurs in
brain due to leak of contrast material from the cut end and oozing blood vessels in brain when
MR imaging is done post- operatively.This is avoided when MIONs are used pre-
operatively.These are rapidly taken up by the tumour cells (Moore et al., 1997), producing long
lasting contrast enhancement of tumour and the remaining nanoparticles are removed from the
circulation by reticuloendothelial system (Weissleder et al., 1989).

20. 20
Magnetic microparticle probes with nanoparticle probes have been used for identification of
proteins like prostate specific antigen. Here magnetic microparticles coated with antibodies
together with nanoprobes with similar coating and a unique hybridized DNA barcode are used.
The microparticle coated with antibody directed against prostate specific antigen combines with
it to form a complex and can be separated by using magnetic separation. The presence of these
separated complexes is determined by dehybridization of the complexed DNA barcode sequence
and polymerase chain reaction for the oligonucleotides. This allows prostate specific antigen
detection at 30 attomolar concentration (Nam et al., 2003).
4.10 Nanosomes
Raoul Kopelman’s group at the University of Michigan, USA, has been working on nanosomes
also called as PEBBLEs (Probes Encapsulated by Biologically Localized Embedding) which
integrate various aspects of medical applications such as targeting, diagnosis and therapy. These
nanosomes are being developed for treatment of various tumours, in particular CNS tumours.
Silica coated iron oxide nanoparticles coated with polyethylene glycol (Xu et al., 2003) and
affixed with targeting antibody and contrast elements like gadolinium are used to access specific
areas of brain involved with tumour. Targeting aids in binding the nanoparticle specifically to the
tumour cells and the contrast elements helps in better detection with magnetic resonance
imaging. Subsequent treatment with laser can destroy the cells loaded with these nanoparticles
by the heat generated by iron oxide particles by absorbing the infra red light. Nanosomes can
also be integrated with a photocatalyst which produces reactive oxygen species when stimulated
by light and destroy the target tissue. This method has advantage over conventional drugs in
being much safer without the adverse effects of cancer chemotherapy drugs and also the absence
of development of drug resistance. Nanosomes are being developed to integrate more and more
components in it for flexibility of its applications (Freitas, 2005).

21. 21
4.11 Dendrimers
Dendrimers are nanostructures produced from macromolecules such as polyamidoamine
(PAMAM), polypropyleneimine and polyaryl ether; and are highly branched with an inner core.
The particle size range is between 1 to 100nm although their sizes are mostly less than 10nm.
About 20 years ago, dendrimer studies centred on their synthesis, physical and chemical
properties while exploration of their biological applications was initiated about thirteen years ago
(Sahoo et al, 2007). The uniqueness of dendrimers is based on their series of
branches,multivalency, well defined molecular weight and globular structure with controlled
surface functionality, which enhances their potential as carriers for drug delivery (Sahoo et al,
2007). Their globular structures and the presence of internal cavities enable drugs to be
encapsulated within the macromolecule interior. Dendrimers have been reported to provide
controlled release from the inner core (Matija, 2004).
Controlled multivalency of dendrimers enables attachment of several drug molecules, targeting
groups and solubilising groups onto the surfaces of the dendrimers in a well defined manner
(Sahoo et al., 2007) Dendrimers are employed due to their size (less than 10nm), ease of
preparation, functionality and their ability to display multiple copies of surface groups for
biological recognition process (Freitas , 2005). Water soluble dendrimers can bind and solubilise
small molecules and can be used as coating agents to protect drugs and deliver to specific sites.
Other applications of dendrimers include catalysis, gene and DNA delivery, biomimetics and as
solution phase supports for combinatorial chemistry (Kostoff et al., 2007).Some of the drug
delivery applications include therapeutic and diagnostic utilization for cancer treatment
(Majumder et al., 2007) enhancement of drug solubility and permeability (dendrimer-drug
conjugates)(Feynman,1960);and intracellular delivery (Smith, 2006).
Dendrimers are also used as contrast agents for imaging.The 1, 4-diaminobutane (DAB) core
dendrimer and the polyamidoamine (PAMAM) dendrimer are well studied commercially
available dendrimers for imaging studies. Renal excretion is the main route of clearance and is
dependent on the size of the particle and more than 60 per cent of injected DAB or PAMAM
dendrimer is cleared from circulation within 15 min (Longmire et al., 2008). Smaller sized

22. 22
dendrimers undergo rapid renal clearance whereas dendrimers with charged surface or
hydrophobic surfaces are rapidly cleared by the liver. Those dendrimers with a hydrophilic
surface escape renal clearance and have a greater circulation time (Duncan and Izzo, 2005).
Cationic dendrimers have a greater potential to cause cytotoxicity compared to anionic
dendrimer or PAMAM dendrimers. It is proposed to cause cell membrane instability and cell
lysis. The toxicity of dendrimer is dependent on the size of the particle and increase with size. It
can be reduced by means of surface modification of the dendrimers with incorporation of PEG or
fatty acids (Svenson and Tomalia, 2005).
4.12 Polymeric nanoparticles
Figure 4. Illustration of Nanospheres,Nanocapsules,Liposomes,Micelles (Svenson and Tomalia ,
2005).
Polymeric nanoparticles are colloidal solid particles with a size range of 10 to 1000nm (Stylios et
al., 2005) and they can be spherical, branched or shell structures. The first fabrication of
nanoparticles was about 35 years ago as carriers for vaccines and cancer chemotherapeutics.
They are developed from non-biodegradable and biodegradable polymers. Their small sizes
enable them to penetrate capillaries and to be taken up by cells, thereby increasing the
accumulation of drugs at target sites. Drugs are incorporated into nanoparticles by dissolution,
entrapment, adsorption, attachment or by encapsulation, and the nanoparticles provide sustained
release of the drugs for longer periods, e.g., days and weeks (Roco, 2003). Nanoparticles

23. 23
enhance immunization by prevention of degradation of the vaccine and increased uptake by
immune cells (Singh et al., 2006). One of the determinants of the extent of uptake by immune
cells is the type of polymer employed. In a study (Miyazaki and Islam, 2007) comparing poly-(_-
caprolactone) (PCL), poly (lactide-coglycolide) (PLGA) and their blend, PCL nanoparticles were
the most efficiently taken up by immune cells due to their hydrophobicity. However, all
polymeric nanoparticles elicited vaccine (diphtheria toxoid) specific serum IgG antibody
response significantly higher than free diphtheria toxoid.
To target drugs to site of action, the drug can be conjugated to a tissue or cell specific ligand or
coupled to macromolecules that reach the target organs. To target an anticancer agent to the
liver, polymeric conjugate nanoparticles which comprised biotin and diamine-terminated poly
(ethylene glycol) with a galactose moiety from lactobionic acid were prepared (Williams, 2008).
Some other applications of nanoparticles include possible recognition of vascular endothelial
dysfunction (Zong et al., 2005);oral deliveryof insulin (Gao et al., 2003); brain drug targeting for
neurodegenerative disorders such as Alzheimer’s disease (Luo et al., 2005); topical
administration to enhance penetration and distribution in and across the skin barrier(Tian et al.,
2007); and pH-sensitive nanoparticles to improve oral bioavailability of drugs such as
cyclosporine A (Shafirovich et al., 2006).
4.13 Solid lipid nanocarriers
Solid lipid nanoparticles (SLN) are nanostructures made from solid lipids such as glyceryl
behenate (Compritol), stearic triglyceride (tristearin), cetyl palmitate and glycerol tripalmitate
(tripalmitin) with a size range of 50 and 1000 nm (Visakhapatnam, 2008). Research interest in
SLN emerged about ten years ago due to their scalability potential. The lipids employed are well
tolerated by the body; large scale production will be cost effective and simple by using high
pressure homogenization. Some of the features of SLN include good tolerability, site-specific
targeting, stability (stabilized by surfactants or polymers), controlled drug release and protection

24. 24
of liable drugs from degradation. However, SLN are known for insufficient drug loading, drug
expulsion after polymorphic transition on storage and relative high water content of the
dispersions. SLN has been studied and developed for parenteral, dermal, ocular, oral, pulmonary
and rectal routes of administration (Zsigmondy, 1926; Roco, 2000-2003; Horton and Khan,
2006;Guo , 2005; Liu et al., 2003).
To overcome the limitations of SLN, nanostructured lipid carriers (NLC) were introduced. NLC
is composed of solid lipids and a certain amount of liquid lipids with improved drug loading and
increased stability on storage thereby reducing drug expulsion (Roco, 2000-2003). NLCs have
been explored for dermal delivery in cosmetics and dermatological preparations (Roco, 2000-
2003).
Lipid drug conjugate (LDC) nanoparticles were introduced to overcome the limitation of types
of drugs incorporated in the solid lipid matrix. Lipophilic drugs are usually incorporated in SLN
but due to partitioning effects during production, only highly potent hydrophilic drugs effective
in low concentrations are incorporated in SLN (Wissing et al., 2004). LDC enables the
incorporation of both hydrophilic (e.g., doxorubicin and tobramycin) and lipophilic (e.g.,
progesterone and cyclosporine A) drugs (Wissing et al., 2004).
4.14 Polymeric micelles
Micelles are formed when amphiphilic surfactant or polymeric molecules spontaneously
associate in aqueous medium to form core-shell structures or vesicles. Polymeric micelles are
formed from amphiphilic block copolymers, such as poly(ethylene oxide)-poly(_-benzyl-
Laspartate) and poly(N-isopropylacrylamide)- polystyrene, and are more stable than surfactant
micelles in physiological solutions (Liu et al., 2003). They were first proposed as drug carriers
about 24 years ago (Liu et al., 2003). The inner core of a micelle is hydrophobic which is
surrounded by a shell of hydrophilic polymers such as poly (ethylene glycol) (Mansoori ,
2002).Their hydrophobic core enables incorporation of poorly water soluble and amphiphilic
drugs while their hydrophilic shell and size (<100nm) prolong their circulation time in the blood
and increase accumulation in tumoural tissues (Liu et al., 2003).

25. 25
Polymeric micelles are able to reach parts of the body that are poorly accessible to liposomes;
accumulate more than free drugs in tumoural tissues due to increased vascular permeability (Liu
et al., 2003). Thus, polymeric micelles can be employed to administer chemotherapeutics in a
controlled and targeted manner with high concentration in the tumoural cells and reduced side
effects. However, the targeting ability of polymeric micelles is limited due to low drug loading
(Balzani, 2005; Teo and Sun, 2006). and low drug incorporation stability (Balzani, 2005). which
cause the loaded drug to be released before getting to the site of action. Consequently,
manipulation of the production parameters and the design of the inner core can improve drug
loading and drug incorporation stability,respectively (Balzani , 2005; Teo and Sun, 2006). Lipid
moieties, such as cholesterol and fatty acyl carnitines, can also be employed to impart good
stability to the polymeric micelles. This is based on increased hydrophobic interaction between
the polymeric chains in the inner core due to presence of fatty acid acyls (e.g.diacyllipid) (Liu et
al., 2003).
Polymeric micelles have been employed for targeted and intracellular delivery (Teo and Sun,
2006) sustained release and parenteral delivery (Liu et al., 2003).
4.15 Nanocapsules
Nanocapsules are spherical hollow structures in which the drug is confined in the cavity and is
surrounded by a polymer membrane (Romig et al., 2007).They were developed over 30 years
ago. Sizes between 50 and 300nm are preferred for drug delivery and they may be filled with oil
which can dissolve lipophilic drugs. They have low density, high loading capacity and are taken
up by the mononuclear phagocyte system, and accumulate at target organs such as liver and
spleen (Shea, 2005).
Nanocapsules can be employed as confined reaction vessels, protective shell for cells or
enzymes, transfection vectors in gene therapy, dye dispersants, carriers in heterogenous catalysis,
imaging and drug carriers (Tratnyek and Johnson , 2006; Roco, 2001). They are known to

26. 26
improve the oral bioavailability of protein and peptides which include insulin, elcatonin and
salmon calcitonin (Romig et al., 2007; Salamanca-Buentello et al., 2005). Encapsulation of drugs
such as ibuprofen(Shea , 2005). within nanocapsules protects liable drugs from degradation,
reduces systemic toxicity, provide controlled release and mask unpleasant taste (Singh, 2007).
Due to their high stability and low permeability, drugs may not be loaded into the capsules after
formulation and also the release of the drug at target site may be difficult. To improve on their
permeability, they are made responsive to physiological factors such as pH (Tegart, 2008).
4.16 Nanoemulsions
Nanoemulsions are emulsions with droplet size below 1μ but usually between 20 and 200nm
(Malsch, 1999; Renn and Roco, 2006). Unlike microemulsions which are white in colour due to
their light scattering ability, nanoemulsions whose nanosize is often smaller than visible
wavelength, are transparent (Malsch, 1999; Dunphy et al., 2000-2004). Nanoemulsions are
biodegradable, biocompatible, easy to produce and used as carriers for lipophilic drugs which are
prone to hydrolysis. They are employed as a sustained release delivery system for depot
formation via subcutaneous injection (Renn and Roco , 2006). They enhance gastrointestinal
absorption and reduce inter- and intra-subject variability for various drugs. Due to their very
large interfacial area, they exhibit excellent drug release profile (Cobb and Macoubrice, 2004).
Nanoemulsions have been studied and developed for parenteral, oral, ocular, pulmonary and
dermal deliveries (Malsch, 1999).
Stability against sedimentation is attained based on the nano size of the droplets because the
sedimentation rate due to gravity is less than Brownian movement and diffusion (Malsch, 1999).
Unlike microemulsions, nanoemulsions are metastable and can be destabilized by Ostwald
ripening whereby the small droplets dissolve and their mass is taken up by the large droplets and
depletion induced flocculation due to addition of thickening polymers. When this happens, the
nanoemulsion becomes opaque and creaming will occur (Roco, 2003). However, addition of a
small amount of a second oil with low solubility into the aqueous phase and addition of a second
surfactant may reduce Ostwald ripening (Malsch, 1999). Also, a number of factors during
production should be controlled (Dunphy et al., 2000-2004). These factors include selecting an

27. 27
appropriate composition, controlling the order of addition of components, applying the shear in a
manner that will effectively rupture the droplets, and ensuring that the dispersed phase molecules
are insoluble in the continuous phase so that Ostwald ripening does not occur rapidly (Dunphy et
al., 2000-2004).
4.17 Ceramic nanoparticles
Ceramic nanoparticles are particles fabricated from inorganic compounds with porous
characteristics such as silica, alumina and titania (Oberdörster et al., 2005; Nimesh et al., 2006;
Soppimath et al., 2001). They can be prepared with the desired size, shape and porosity. Their
sizes are less than 100nm and are able to avoid uptake by the reticulo-endothelial system as
foreign bodies. Entrapped molecules such as drugs, proteins and enzymes are protected from
denaturation at physiological pH and temperature as neither swelling nor change in porosity
occurs (Soppimath et al., 2001).Hence, they are effective in delivering proteins and genes.
However, these particles are not biodegradable and so there is concern that they may accumulate
in the body and cause harmful effects (Nimesh et al., 2006).
4.18 Metallic nanoparticles
Metallic nanoparticles include iron oxide, gold, silver, gadolinium and nickel which have been
studied for targeted cellular delivery(Jung et al., 2000).Gold exhibits favourable optical and
chemical properties at nanoscale for biomedical imaging and therapeutic applications (Nimesh et
al., 2006). It can be manipulated to obtain the desired size in the range of 0.8 to 200nm. The
surface can be modified with different functional groups for gene transfection, modified into
gene delivery vector by conjugation and also modified to target proteins and peptides to the cell
nucleus (Jung et al., 2000; Italia et al., 2007). Gadolinium has been studied for enhanced tumour
targeted delivery by modification of the nanoparticles with folate, thiamine and poly (ethylene
glycol). Modification with folate was reported to enhance the recognition, internalization and
retention of gadolinium nanoparticles in tumour cells (Jung et al., 2000).

28. 28
4.19 Carbon nanomaterials
These include carbon nanotubes and fullerenes. Fullerenes are carbon allotrope made up of 60 or
more carbon atoms with a polygonal structure. Nanotubes have been used for their high electrical
conductivity and excellent strength (Nimesh et al., 2006). These materials are being studied for
therapeutic applications. Fullerenes can be functionalized for delivery of drugs and biomolecules
across cell membrane to the mitochondria (Jung et al., 2000). Carbon nanotubes’ unique
properties including low cytotoxicity and good biocompatibility attract their use as vector system
in target delivery of drugs, proteins and genes (Jung et al., 2000). However,toxicity of carbon
nanotubes is of concern (Sahoo and Labhasetwar, 2003). Carbon nanotubes may cause
inflammatory and fibrotic reactions.
Figure 5: Illustration of some nanostructures A) Spherical polymeric nanoparticle; B) Liposome;
C)Solid lipid nanoparticles – solid lipid enclosed within; D) Nanoemulsion – liquid enclosed
within; E)Nanocapsule – hollow; F) Carbon nanotube; G) Dendrimer; I) Polymeric micelle.
(Ochekpe et al., 2009).

29. 29
5. Nanosurgery
Present-day nanomedicine exploits carefully structured nanoparticles such as dendrimers (Borges
and Schengrund, 2005), carbon fullerenes (buckyballs) (Mashino et al., 2005) and Nanoshells
(O’Neal et al., 2004) to target specific tissues and organs. These nanoparticles may serve as
diagnostic and therapeutic antiviral, antitumor or anticancer agents. But as this technology
matures in the years ahead, complex nanodevices and even nanorobots will be fabricated, first of
biological materials but later using more durable materials such as diamond to achieve the most
powerful results.
5.1 Early vision
The first and most famous scientist to voice this possibility was the late Nobel physicist Richard
P. Feynman. In his remarkably prescient 1959 talk ‘‘There’s Plenty of Room at the Bottom,’’
Feynman proposed employing machine tools to make smaller machine tools, these are to be used
in turn to make still smaller machine tools, and so on all the way down to the atomic level,
noting that this is ‘‘a development which I think cannot be avoided.’’ (Feynman, 1960)
Feynman was clearly aware of the potential medical applications of this new technology. He
offered the first known proposal for a nanorobotic surgical procedure to cure heart disease: ‘‘a
friend of mine (Albert R. Hibbs) suggests a very interesting possibility for relatively small
machines. He says that, although it is a very wild idea, it would be interesting in surgery if you
could swallow the surgeon. You put the mechanical surgeon inside the blood vessel and it goes
into the heart and looks around. (Of course the information has to be fed out.) It finds out which
valve is the faulty one and takes a little knife and slices it out. .[Imagine] that we can
manufacture an object that maneuvers at that level!. Other small machines might be permanently
incorporated in the body to assist some inadequately functioning organ.’’ (Feynman, 1960)

30. 30
5.2 Medical microrobotics
There are ongoing attempts to build microrobots for in vivo medical use. In 2002, at Tohoku
University developed tiny magnetically driven spinning screws intended to swim along veins and
carry drugs to infected tissues or even to burrow into tumors and kill them with heat (Freitas,
2005). In 2003, the ‘‘MR-Sub’’ project of Martel’s group at the NanoRobotics Laboratory of
Ecole Polytechnique in Montreal tested using variable MRI magnetic fields to generate forces on
an untethered microrobot containing ferromagnetic particles, developing sufficient propulsive
power to direct the small device through the human body (Freitas, 2005). Brad Nelson’s team at
the Swiss Federal Institute of Technology in Zurich continued this approach. In 2005, they
reported the fabrication of a microscopic robot small enough (w200 mm) to be injected into the
body through a syringe. They hope that this device or its descendants might someday be used to
deliver drugs or perform minimally invasive eye surgery (Freitas, 2005). Nelson’s simple
microrobot has successfully maneuvered through a watery maze using external energy from
magnetic fields, with different frequencies that are able to vibrate different mechanical parts on
the device to maintain selective control of different functions. Gordon’s group at the University
of Manitoba has also proposed magnetically controlled ‘‘cytobots’’ and ‘‘karyobots’’ for
performing wireless intracellular and intranuclear surgery (Freitas, 2005).
5.3 Manufacturing medical nanorobots
The greatest power of nanomedicine will emerge, perhaps in the 2020s, when we can design and
construct complete artificial nanorobots using rigid diamondoid nanometer-scale parts like
molecular gears (Fig. 8) and bearings (Freitas , 2005).

31. 31
Figure 6. A molecular planetary gear is a mechanical component that might be found inside a
medical nanorobot. The gear converts shaft power from one angular frequency to another. The
casing is a strained silicon shell with predominantly sulfur termination, with each of the nine
planet gears attached to the planet carrier by a carbon-carbon single bond. The planetary gear
shown here has not been built experimentally but has been modeled computationally.
5.4 Respirocytes and microbivores
The ability to build complex diamondoid medical nanorobots to molecular precision, and then to
build them cheaply enough in sufficiently large numbers to be useful therapeutically, will
revolutionize the practice of medicine and surgery (Freitas, 2005).The first theoretical design
study of a complete medical nanorobot ever published in a peer-reviewed journal (in 1998)
described a hypothetica l artificial mechanical red blood cell or ‘‘respirocyte’’ made of 18 billion
precisely arranged structural atoms (Freitas, 1998). The respirocyte is a bloodborne spherical 1-
mm diamondoid 1000-atmosphere pressure vessel with reversible molecule-selective surface
pumps powered by endogenous serum glucose. This nanorobot would deliver 236 times more
oxygen to body tissues per unit volume than natural red cells and would manage carbonic
acidity, controlled by gas concentration sensors and an onboard nanocomputer. A 5-cc

32. 32
therapeutic dose of 50% respirocyte saline suspension containing 5 trillion nanorobots could
exactly replace the gas carrying capacity of the patient’s entire 5.4 l of blood.
Nanorobotic artificial phagocytes called ‘‘microbivores’’ (Fig. 9)
Figure 7. Nanorobotic artificial phagocytes called ‘‘microbivores’’could patrol the bloodstream,
seeking out and digesting unwanted pathogens (Freitas, 2005).
Could patrol the bloodstream, seeking out and digesting unwanted pathogens including bacteria,
viruses, or fungi (Freitas, 2005).
6. Nanotechnology in drug delivery
Generally, nanostructures have the ability to protect drugs encapsulated within them from
hydrolytic and enzymatic degradation in the gastrointestinal tract; target the delivery of a wide
range of drugs to various areas of the body for sustained release and thus are able to deliver
drugs, proteins and genes through the peroral route of administration (Nimesh et al., 2006;
Soppimath et al., 2001; Jung et al., 2000). They deliver drugs that are highly water insoluble; can
bypass the liver, thereby preventing the first pass metabolism of the incorporated drug (Italia et
al., 2007; Sahoo and Labhasetwar , 2003). They increase oral bioavailability of drugs due to
their specialized uptake mechanisms such as absorptive endocytosis and are able to remain in the

33. 33
blood circulation for a longer time, releasing the incorporated drug in a sustained and continuous
manner leading to less plasma fluctuations thereby minimizing side-effects caused by drugs
(Italia et al., 2007). Due to the size of nanostructures, they are able to penetrate into tissues and
are taken up by cells, allowing efficient delivery of drugs to sites of action. The uptake of
nanostructures was found to be 15-250 times greater than that of microparticles in the 1-10μm
range (Panyam and Labhasetwar , 2003).
Through the manipulation of the characteristics of polymers, release of drug from nanostructures
can be controlled to achieve the desired therapeutic concentration for the desired duration. For
targeted delivery, nanostructures can be conjugated with targeting moieties such that the linkage
between the polymer and the active substance can be manipulated to control the site and duration
at which the drug is released. The linkage may be achieved by incorporation of amino acids,
lipids, peptides or small chains as spacer molecules (Peppas, 2004). Drug targeting is crucial in
chemotherapy, where a drug delivery system can target only the malignant tumour while
shielding the healthy cells from uniform distribution of chemotherapeutics in the body and their
harmful effects.
The use of nanostructures such as polymeric nanoparticles is a non-invasive approach of
penetrating the blood brain barrier for management of neurodegenerative disorders,
cerebrovascular and inflammatory diseases (Garcia-Garcia et al., 2005; Ringe et al., 2004).
Research and development of new drugs are capital- and time- intensive which requires that
pharmaceutical companies, in addition,search for other means of meeting up with market
demands. New drug delivery methods enable pharmaceutical companies reformulate existing
drugs in the market. Nanotechnology is strategic in developing drug delivery systems which can
expand drug markets. Nanotechnology can be applied to reformulate existing drugs thereby
extending products’ lives, enhance their performance, improve their acceptability by increasing
effectiveness, as well as increase safety and patient adherence, and ultimately reduce health care
costs (Sahoo and Labhasetwar, 2003; Hughes, 2005). Nanotechnology may also enhance the
performance of drugs that are unable to pass clinical trial phases (Hughes, 2005). It provides

34. 34
drug delivery carriers, as well as treatment and management of chronic diseases which include
cancer, HIV/AIDS and diabetes.
Table 2
Examples of drug delivery technologies in relation to the current nanotechnology revolution
(Hughes , 2005).
Period Before Nanotechnology
(Past)
Transition Period
(Present)
Mature
Nanotechnology
(Future)
Technology Emulsion-based
preparation of nano/micro
particles
Nano/micro fabrication Nano/micro
manufacturing
Examples • - Liposomes
• -Polymer micelles
• - Dendrimers
• - Nanoparticles
• - Nanocrystals
• - Microparticles
• -Microchip
systems
• -Microneedle
transdermal
delivery systems
• - Layer-by-layer
assembled systems
• - Microdispensed
particles
• -Nano/micro
machines for
scale-up
production
7. Commercially available nano drug delivery systems
Despite the challenges which include the huge volume of expenditure involved and the
regulatory stages (preclinical and clinical stages – Phases 1 - 4) which are mandatory in order to
obtain regulatory approval before a drug can get into the market, some nano drug delivery
systems have made it to the market. Table 3 shows the list of some of nano drug delivery
systems in the market:

35. 35
Table 3: Nano drug delivery systems in the market(Wagner et al., 2006)

36. 36
8. Conclusion
The nanotechnology will help to improve health by enhancing the efficacy and safety of
nanosystems and nanodevices. Moreover, early diagnosis, implants with improved properties,
cancer treatment and minimum invasive treatments for heart disease, diabetes and other diseases
are anticipated. In the coming years, nanotechnology will play a key role in the medicine of
tomorrow providing revolutionary opportunities for early disease detection, diagnostic and
therapeutic procedures to improving health and enhancing human physical abilities, and enabling
precise and effective therapy tailored to the patient. Nanomedicine is in infancy, having the
potential to change medical research dramatically in the 21st century. Nanomedical devices can
be applied for analytical, imaging, detection, diagnostic and therapeutic purposes and
procedures, such as targeting cancer, drug delivery, improving cell-material interactions,
scaffolds for tissue engineering, and gene delivery systems, and provide innovative opportunities
in the fight against incurable diseases. Many novel nanoparticles and nanodevices are expected
to be used, with an enormous positive impact on human health. Over the next ten to twenty years
nanotechnology may fundamentally transform science, technology, and society offering a
significant opportunity to enhance human health in novel ways, especially by enabling early
disease detection and diagnosis, as well as precise and effective therapy tailored to the patient.

37. 37
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