Nanotechnology in medical sciences

NANOTECHNOLOGY IN MEDICAL SCIENCES

NANOMEDICINE

Nanomedicine is the medical application of nanotechnology. In the near future,

advancement in nanomedicine will deliver a valuable set of research tools and clinically
helpful devices.

The National Nanotechnology Initiative expects new commercial applications in the

pharmaceutical industry that will include advanced drug delivery systems, new therapies,
and in vivo imaging. Farther down the line, neuro-electronic interfaces and cell repair
machines could revolutionize medicine and the medical field, but now nanomedicine is
becoming one of the biggest industries in the world. In 2004, nanomedicine sales reached
6.8 billion dollars, and with over 200 companies and 38 products worldwide, a minimum
of 3.8 billion dollars in nanotechnology R&D is being invested every year.

As the nanomedicine industry continues to grow, there is no doubt that it will have a
significant impact on the economy. The most important innovations are taking place in
drug delivery which involves developing nanoscale particles or molecules to improve
bioavailability. Bioavailability refers to the presence of drug molecules where they are
needed in the body and where they will do the most good. Drug delivery focuses on
maximizing bioavailability both at specific places in the body and over a period of time.
Over 65 billion dollars is wasted every year because of poor bioavailability.

In vivo imaging is another area where tools and devices are being developed. Using
nanoparticle contrast agents, images such as ultrasound and MRI have a favorable
distribution and improved contrast. The new therapies and surgeries that are being
developed might be effective in treating illnesses and diseases such as cancer. Finally, a
shift from the possible to the potential will be made when nanorobots such as neuro-
electronic interfaces and cell repair machines are discussed.4

28
 Nanotechnology in medical sciences

Smart Drugs

Nanobodies® like Antibodies but smaller10

Nanobodies® are a novel class of antibody-derived therapeutic proteins. Because of their

small size, unique structure and unparalleled stability, Nanobodies® combine the
advantages of conventional antibody therapeutics with key features of small-molecule
drugs.

NanoCrystal® Technology10

Poor water solubility correlates with slow dissolution rate and decreasing particle size
increases the surface area which leads to an increase in dissolution rate. This can be
accomplished predictably and efficiently using NanoCrystal technology. NanoCrystal
particles are small particles of drug substance, typically less than 1000 nanometers (nm)
in diameter, which are produced by milling the drug substance using a proprietary wet-
milling technique.
The NanoCrystal technology can be incorporated into all dosage forms both parenteral
and oral, including solid, liquid, fast-melt, pulsed release and controlled release dosage
forms

Drug Delivery11

29
 Nanotechnology in medical sciences

Drug delivery systems, lipid- or polymer-based nanoparticles, can be designed to

improve the pharmacological and therapeutic properties of drugs. The strength of drug
delivery systems is their ability to alter the pharmacokinetics and biodistribution of the
drug.

Nanoparticles have unusual properties that can be used to improve drug delivery. Where
larger particles would have been cleared from the body, cells take up these nanoparticles
because of their size. Complex drug delivery mechanisms are being developed, including
the ability to get drugs through cell walls and into cells.

Efficiency is important because many diseases depend upon processes within the cell
and can only be impeded by drugs that make their way into the cell. Triggered response is
one way for drug molecules to be used more efficiently. Drugs are placed in the body and
only activate on encountering a particular signal. For example, a drug with poor solubility
will be replaced by a drug delivery system where both hydrophilic and hydrophobic
environments exist, improving the solubility. Also, a drug may cause tissue damage, but
with drug delivery, regulated drug release can eliminate the problem. If a drug is cleared
too quickly from the body, this could force a patient to use high doses, but with drug
delivery systems clearance can be reduced by altering the pharmacokinetics of the drug.

Nanomedicines have a size range that allows them to be injected without occluding
needles and capillaries and are ideal for targeted drug delivery and medical imaging due
to the pathophysiology of certain disorders such as cancer and inflammation.

The main nanoscale systems are

• liposomes
• phospholipids
• pluronic
• poly (L-aminoacid)
• polyester

30
 Nanotechnology in medical sciences

• nanoemulsions
• nanoparticulate systems
• Drug nanocrystals.
• polymer based nanoparticles
• lipid based nanoparticles
• ceramic based nanoparticles
• albumin nanoparticles
• nanogels
• dendrimers.

The nanocarrier systems possess multiple desirable attributes:

1. When drugs and imaging agents are associated with nanoscale carriers, their volumes
of distribution are reduced. Nanoscale drug delivery systems also have the ability to
improve the pharmacokinetics and increase biodistribution of therapeutic agents to target
organs, which will result in improved efficacy.
2. Drug toxicity is reduced as a consequence of preferential accumulation at target sites
and lower concentration in healthy tissues. Nanocarriers have been designed to target
tumors and inflammation sites that have permeable vasculature.
3. Nanocarriers have the desirable advantage of improving solubility of hydrophobic
compounds in the aqueous medium to render them suitable for parenteral administration
4. Delivery systems have been shown to increase the stability of a wide variety of
therapeutic agents such as small hydrophobic molecules, peptides, and oligonucleotides.
5. Nanocarriers composed of biocompatible materials are investigated as safe alternatives
to existing vehicles, which may cause hypersensitivity reactions and peripheral
neuropathy.
Nanowires Can Help Monitor Blood Pressure 7

Changes in body blood pressure can be monitored using ‘nanowires’. A new class of
components have been created using the piezoelectric effect in semi-conducting zinc
oxide nanowires.

31
 Nanotechnology in medical sciences

These nanowires can detect forces as small as a few piconewtons (10-12

N). It is roughly the force required for “unzipping” a DNA strand. A
piezoelectric effect can produce a current when they are bent.

Nanorobots

An artificially fabricated object able to freely diffuse in the human body & interact with
specific cell at the molecular level by itself. (L. levy –2000)

• Used for the purpose of maintaining and protecting the human body against
pathogens.

• Diameter of about 0.5 to 3 microns and will be constructed out of parts with
dimensions in the range of 1 to 100 nanometers.

• The main element used will be carbon in the form of diamond / fullerene
nanocomposites

Robert A. Freitas has described how medical nanorobots might utilise specific motility
mechanisms to crawl or swim through human body tissues with navigational precision,
acquire energy, sense and manipulate their surroundings, achieve safe cytopenetration
(e.g., pass through plasma membranes such as the odontoblastic process without
disrupting the cell), and employ any of a multitude of techniques to monitor, interrupt, or
alter nerve impulse traffic in individual nerve cells in real time. These nanorobot

32
 Nanotechnology in medical sciences

functions may be controlled by an onboard nanocomputer executing preprogrammed

instructions in response to local sensor stimuli.2

To cure skin diseases, a cream containing nanorobots may be used. It could remove the
right amount of dead skin, remove excess oils add missing oils, apply the right amounts
of natural moisturizing compounds, achieve the elusive goal of 'deep pore cleaning' by
actually reaching down into pores and cleaning them out.

Augment the immune system by finding and disabling unwanted bacteria and viruses.
When an invader is identified it can be punctured, letting its contents spill out and ending
its effectiveness. If the contents were known to be hazardous by themselves, then the
immune machine could hold on to it long enough to dismantle it more completely

In the bloodstream it could remove/dissolve away at arteriosclerotic deposits, widening

the affected blood vessels, restore artery walls and artery linings to health, by ensuring
that the right cells and supporting structures are in the right places. This would prevent
most heart attacks.4

Cancer therapy

33
 Nanotechnology in medical sciences

A schematic illustration showing how nanoparticles or other other cancer drugs might be
used to treat cancer.

Nanoparticles of cadmium selenide (quantum dots) glow when exposed to ultraviolet

light. When injected, they seep into cancer tumors. The surgeon can see the glowing
tumor, and use it as a guide for more accurate tumor removal.

Sensor test chips containing thousands of nanowires, able to detect proteins and other
biomarkers left behind by cancer cells, could enable the detection and diagnosis of cancer
in the early stages from a few drops of a patients blood.4

34
 Nanotechnology in medical sciences

New sensor for ph determination

pH may be useful in determining whether or not some cancer tumors are malignant. With
current methods, a piece of the tumor would need to be physically removed via biopsy –
a painful and invasive procedure – and visually evaluated under a microscope. nano-pH
meter could be used instead as an "optical biopsy" to measure the pH inside the tumor
with nothing more invasive than an injection.7

In vivo/ Therapy

Medical nanodevices would first be injected into a human body, and would then go to
work in a specific organ or tissue mass. The doctor will monitor the progress, and make
certain that the nanodevices have gotten to the correct target treatment region. The doctor
wants to be able to scan a section of the body, and actually see the nanodevices
congregated neatly around their target (a tumor mass, etc.) so that he or she can be sure
that the procedure was successful. Tracking movement can help determine how well
drugs are being distributed or how substances are metabolized. It is difficult to track a
small group of cells throughout the body so scientists used to dye the cells. These dyes
needed to be excited by light of a certain wavelength in order for them to light up. While
different color dyes absorb different frequencies of light, there was a need for as many
light sources as cells. A way around this problem is with luminescent tags.

These tags are quantum dots attached to proteins that penetrate cell walls. The dots can be
random in size, can be made of bio-inert material, and they demonstrate the nanoscale
property that color is size-dependent. As a result, sizes are selected so that the frequency

35
 Nanotechnology in medical sciences

of light used to make a group of quantum dots fluoresce is an even multiple of the
frequency required to make another group incandesce.4

Neuro-electronic Interfaces

Neuro-electronic interfaces are a visionary goal dealing with the construction of

nanodevices that will permit computers to be joined and linked to the nervous system.
This idea requires the building of a molecular structure that will permit control and
detection of nerve impulses by an external computer.

The computers will be able to interpret, register, and respond to signals the body gives off
when it feels sensations. The demand for such structures is huge because many diseases
involve the decay of the nervous system (ALS and multiple sclerosis). Also, many
injuries and accidents may impair the nervous system resulting in dysfunctional systems
and paraplegia. If computers could control the nervous system through neuro-electronic
interface, problems that impair the system could be controlled so that effects of diseases
and injuries could be overcome.4

36
 Nanotechnology in medical sciences

Cell repair machines

Using drugs and surgery, doctors can only encourage tissues to repair themselves. With
molecular machines, there will be more direct repairs. Cell repair will utilize the same
tasks that living systems already prove possible. Access to cells is possible because
biologists can stick needles into cells without killing them. Thus, molecular machines are
capable of entering the cell. Also, all specific biochemical interactions show that
molecular systems can recognize other molecules by touch, build or rebuild every
molecule in a cell, and can disassemble damaged molecules. Finally, cells that replicate
prove that molecular systems can assemble every system found in a cell. Therefore, since
nature has demonstrated the basic operations needed to perform molecular-level cell
repair, in the future, nanomachine based systems will be built that are able to enter cells,
sense differences from healthy ones and make modifications to the structure.

Nanocomputers will be needed to guide these machines. These computers will direct
machines to examine, take apart, and rebuild damaged molecular structures. Repair
machines will be able to repair whole cells by working structure by structure. Then by

37
 Nanotechnology in medical sciences

working cell by cell and tissue by tissue, whole organs can be repaired. Finally, by
working organ by organ, health is restored to the body.4

Tissue Engineering and nanotechnology12

Tissue engineering, as an emerging and rapidly growing field, has received extensive
attention. The ultimate goal of tissue engineering as a treatment concept is to replace or
restore the anatomic structure and function of damaged, injured, or missing tissue or
organs following any injury or pathological process by combining biomaterials, cells, or
tissue, biologically active molecules, and/or stimulating mechanical forces of the tissue
microenvironment

Biomaterials are fashioned into three-dimensional scaffolds to provide mechanical

support and guide cell growth into new tissues or organs. The scaffolds have to be highly
porous to allow seeding of cells at high densities and, upon implantation into the body, to
facilitate the infiltration and formation of large numbers of blood vessels for nutrient
supply of the transplanted cells and the removal of waste products. The extracellular
matrix deposited by the cells confers the physical, mechanical, and functional properties
of the tissue or organ.

To date, most tissue engineering studies are focused on the investigations of macrolevel
structures (e.g., supercelluar structures >100 µm and cellular structures >10 µm) to build
the essential gross morphology and generate real-size organ systems. However, to
ultimately engineer the functional units of the tissue, not only the supercelluar and
cellular scale structures but also the subcellular scale structures (0.1–10 µm) and
nanostructures (1–100 nm) need to be constructed to control cellular environment, cell–

38
 Nanotechnology in medical sciences

molecular interactions, and cell–cell interactions. It is quite obvious that the full function
of the tissues and organs cannot be recovered without rebuilding the ultrastructures of the
tissue itself.

Applications of nanotechnology in Tissue engineering

.
Tissue engineering at different levels.

A biomaterial scaffold creates a milieu within which cells are instructed to form a tissue
or organ in a highly controlled way. The principal function of a scaffold is to direct cell
behaviors such as migration, proliferation, differentiation, maintenance of phenotype, and
apoptosis, by facilitating sensing and responding to the environment via cell–matrix
communications and cell–cell communications. Therefore, the desirable physical
characteristics of biomaterial scaffolds for tissue engineering applications include high
porosity, large surface area, large pore size, and uniformly distributed interconnected
porous structures throughout the matrix. In addition, the scaffold has to provide spatial
signals to modulate the organization of the cells as well as that of the extracellular matrix
derived from them.

Using nanotechnology, biomaterial scaffold can be manipulated at atomic, molecular, and

macromolecular levels and constructed into specific geometrical and topological
structures at 1–100 nm scales. Creating tissue engineering scaffolds in nanoscale may

39
 Nanotechnology in medical sciences

bring unpredictable new properties to the material, such as mechanical (stronger),

physical (lighter and more porous), optical (tunable optical emission), color, chemical
reactivity (more active or less corrosive), electronic properties (more electrically
conductive), or magnetic properties (superparamagnetic) and may come up with new
functionalities as well, which are unavailable at micro- or macroscales .

Other advantages of using nanotechnology for scaffold fabrication may include

enhancing biocompatibility, improving contact guidance, reducing friction and therefore
wear for joint applications, reducing the need for revision surgery, altering physical or
chemical characteristics of the scaffold, and promoting tissue growth around the implant.
For example, it has been found that nanosculpting the surface of such scaffolds
may stimulate cell growth; the cells rapidly follow the nanoscopic etched tracks, resulting
in a faster filling of the matrix with the required cells or tissues . More importantly, some
complex specific tissue functions cannot be easily mimicked with macroresolution
scaffolds.

Nanoscale precision scaffolds can be built in three ways, i.e., atom-by-atom, molecule-
bymolecule (also called top-down), or self-assembly (also called self-organization or
bottomup). Top-down means fabricating nanodevices from the microlevel to the
nanolevel, for example, stripping a virus particle down to form a viral cage; while
bottom-up means obtaining nanodevices from the atoms and small molecules at a level
smaller than the nanolevel, for example, building supermolecular architectures from
single small molecules, even single atom.

40
 Nanotechnology in medical sciences

Nanotechnology Clear Clogged Arteries7

Heart patients are set to benefit from nanotechnology by using this technology for
clearing clogged and clogging arteries with the help of lasers.

Nanotechnology coupled with laser machines has also helped in reducing the side effects
attributed with laser. In the case of laser at times remnants are left behind which tend to
get hardened over a period of time. Patients suffering from arterial conditions which are
caused due to diabetes, smoking or other conditions are subjected to this surgical
procedure.

Damaged arteries in extreme cases can lead to gangrene or debilitating conditions and
nanotechnology has been found out to be effective in clearing clogged arteries and
minimize the side effects of laser therapy.

41
 Nanotechnology in medical sciences

Bones to Be Grown with Nanotechnology7

A new nanoscale biocomposite has been developed by scientists in Singapore which will
help in mimicking the extracellular matrix architecture. For this purpose electrospinning
technique was used for fabricating polycaprolactone/nanohydroxyapatite/collagen
biocomposite nanofibrous scaffolds which would offer mechanical support and lead to
the growth of human fetal osteoblasts.

This scaffold would be offering structural integrity within the body and ultimately
breakdown leaving behind the neo-tissue which will be instrumental in repairing the
diseased tissues and organs.

42