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 International Journal on Current Trends in Drug Development & Industrial Pharmacy
Vol 2, Issue 2 - 2017
NANOMEDICINE AND NANOTECHNOLOGY:
THE FUTURE OF PHARMACY
SURAJ KUMAR PRAJAPATI*, SWETHA SRIVASTAV*, MANOJ KUMAR MISHRA*

ABSTRACT

Nanomedicine can address many important medical problems by using

nanoscale-structured materials and simple nanodevices that can be
manufactured today, including the interaction of nano-structured materials with
biological systems. Nanoparticles with an even greater range for the early
detection and therapy of brain cancer, using silica-coated iron oxide
nanoparticles with a biocompatible polyethylene glycol coating. The miniscule
size of the particles 20-200 nanometres should allow them to penetrate into
areas of the brain that would otherwise be severely damaged by invasive
surgery. The particles are attached to a cancer cell antibody or other tracer
molecule that adheres to cancer cells, and are affixed with a nanopacket of
contrast agent that makes the particles highly visible during magnetic resonance
imaging (MRI).The particles also enhance the killing effect during the subsequent
laser irradiation of brain tissue, concentrating the destructive effect only on sick
cells unlike traditional chemotherapy and radiation which kills cancerous cells
but also destroys healthy cells. Nanoparticles allow MRI to see a few small brain
tumor cells as small as 50 microns depending on the cancer type, tumor cells can
range from 5-50 microns each and may grow in locations separate from the
tumor site.

KEYWORDS: Nanomedicine, Nanoparticles, MRI, Nanopacket.

INTRODUCTION

Nanomedicine, for the purpose of this document the nanometer scale. Nanomedicine has the
is defined as the application of nanotechnology potential to enable early detection and
to achieve breakthroughs in healthcare. It prevention, and to essentially improve diagnosis,
exploits the improved and often novel physical, treatment and follow-up of diseases.
chemical and biological properties of materials at

*
Shambhunath Institute of Pharmacy Jhalwa, Allahabad, Uttar Pradesh-211012, India.
Correspondence E-mail Id: editor@eurekajournals.com

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Nanomedicine and Nanotechnology: The Future of Pharmacy
Suraj KP et al. 2

Figure 1.Introduction of Nanomedicines

NANOPORE control feedback loop without the need for

powerful immuno-suppressants that can leave
Perhaps one of the simplest medical the patient at serious risk for infection. Supplying
Nanomaterials is a surface perforated with holes, encapsulated new cells to the body could also be
or nanopores. Desaiand Ferrari created what a valuable way to treat other enzyme or hormone
could be considered one of the earliest deficiency diseases [2] including encapsulated
therapeutically useful nanomedical devices [1] neurons which could be implanted in the brain
employing bulk micromachining to fabricate tiny and then be electrically stimulated to release
cell-containing chambers within single crystalline neurotransmitters, possibly as part of a future
silicon wafers. The chambers interface with the treatment for Alzheimer’s or Parkinson’s
surrounding biological environment through diseases. The flow of materials through
polycrystalline silicon filter membranes which are nonporous can also be externally regulated
micro-machined to present a high density of [3].The first artificial voltage-gatedmolecular
uniform nanopores as small as 20 nanometres in nanosieve was fabricated by Martin and
diameter. These pores are large enough to allow colleagues in 1995 experiments with new 3–10
small molecules such as oxygen, glucose, and nm silicon-nitride nanopores and investigating
insulin to pass, but are small enough to impede the benefits of adding electrically conducting
the passage of much larger immune system electrodes to pores to improve longitudinal
molecules such as immune globulins and graft- resolution “possibly to the single-base level for
borne virus particles. Safely ensconced behind DNA” [4].Nan pore-based DNA sequencing
this artificial barrier, immune isolated devices could allow per-pore read rates
encapsulated rat pancreatic cells may receive potentially up to 1000 bases per second possibly
nutrients and remain healthy for weeks, secreting eventually providing a low-cost high-throughput
insulin back out through the pores while the method for very rapid genome sequencing.
immune system remains unaware of the foreign
cells which it would normally attack and reject. QUANTUM DOTS AND NANOCRYSTALS

Microcapsules containing replacement islets of Fluorescent tags are commonplace in medicine

Langerhans cells: Most likely easily-harvested and biology, found in everything from HIV tests to
piglet islet cells could be implanted beneath the experiments that image the inner functions of
skin of some diabetes patients. This could cells. But different dye molecules must be used
temporarily restore the body’s delicate glucose for each color, color-matchedlasers are needed

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 International Journal on Current Trends in Drug Development & Industrial Pharmacy
3 Vol 2, Issue 2 - 2017

to get each dye to fluoresce, and dyecolors tend measuring only a few nanometers across, about
to bleed together and fade quickly after one use. the same size as a protein molecule or a short
“Quantum dot” nanocrystals have none of these sequence of DNA.
shortcomings. These dots are tiny particles

Figure 2.Types of nanocrystals

They come in an early unlimited palette of for the development of future pharmaceuticals
sharply-defined colors which can be customized and therapeutics. Quantum dots are useful for
by changing particle size or composition. Particles studying genes, proteins and drug targets in
can be excited to fluorescence with white light, single cells, tissue specimens, and living animals.
can be linked to biomolecules to form long-lived Quantum dots are being investigated as chemical
sensitive probes to identify specific compounds sensors for cancer cell detection. gene expression
up to athous and times brighter than studies gene mapping and DNA [6] microarray
conventional dyes used in many biological tests, analysis immune cytochemical probes
and can track biological events by simultaneously intracellular organelle markers live cell labelling
tagging each biological component (e.g., different medical diagnostics and drug screening SNP
proteins or DNA sequences) with nanodots of as (Single Nucleotide Polymorphism) genotyping
pecific color. Quantum Dot Corp. the vascular imaging and many other applications.
manufacturer believes this kind of flexibility could Quantum dot physics has been studied
offer a cheap and easy way to screen a blood theoretically and computationally using time-
sample for the presence of a number of different dependent density functional theory and other
viruses at the same time. It could also give method.
physicians a fast diagnostic tool to detect say the
presence of a particular set of proteins that FULLERENESAND NANOTUBES
strongly indicates a person is having a heart
Soluble derivatives of fullerenes such as C60 have
attack or to detect known cellular cancer markers
shown great utility as pharmaceutical agents.
[5].On the research front, the ability to
These derivatives, many already in clinical trials
simultaneously tag multiple biomolecules both on
have good biocompatibility and low toxicity even
and inside cells could allow scientists to watch
at relatively high dosages. Fullerene compounds
the complex cellular changes and events
may serve as antiviral agents (most notably
associated with disease, providing valuable clues
against HIV [7], where they have also been

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Nanomedicine and Nanotechnology: The Future of Pharmacy
Suraj KP et al. 4

investigated computationally, antibacterial Single-walled and multi-walled carbon nano

agents (E. Coli [8], Streptococcus [9], tubes are being investigated as biosensors for
Mycobacteriumtuberculosis.10etc.), photodynamic example to detect glucose ethanol hydrogen
antitumor and anticancer therapies, antioxidants peroxide selected proteins such as immune
and anti-apoptosis agents which may include globulins and as an electrochemical DNA
treatments for amyotrophic laterals clerosis (ALS hybridization biosensor [10].
or Lou Gehrig’s disease)and Parkinson’s disease.

Figure 3.Nanoparticle- based carriers

NANOSHELLSAND MAGNETIC NANOPROBES size infrared laser to heat the skin where the
nanoshell polymer had been injected.
Unlike carbon fullerenes, the slightly largernano
shells are dielectric-metal nanospheres with a The heat from nanoshells would cause the
core of silica and a gold coating, whose optical polymer to release a pulse of insulin. Unlike
resonance is a function of the relative size of the injections, which are taken several times a day,
constituent layers. The nanoshells are embedded the nanoshell-polymer system could remain in
in a drug-containing tumor targeted hydrogel the body for months. Nanospectra is conducting
polymer and injected into the body. The shells animal studies at the MDAnderson Cancer Centre
circulate through the body until they accumulate at the University of Texas, specifically targeting
near tumor cells. When heated with an infrared micro metastases, tiny aggregates of cancer cells
laser, the nanoshells (each slightly larger than a too small for surgeons to find and remove with a
polio virus) selectively absorb the IR frequencies, scalpel. Varying the thickness of the metal shell
melt the polymer and release their drug payload allow precise tuning of the color of light to which
at a specific site. Nanoshells [11] offer advantages the nanoshells respond; near-infrared light
over traditional cancer treatments: earlier penetrates whole blood very well, so it is an
detection, more detailed imaging, fast non- optimal wavelength for whole blood
invasive imaging, and integrated detection and immunoassay. Successful detection of sub-
treatment. This technique could also prove useful nanogram-per-millilitre quantities of
in treating diabetes. Instead of taking an injection immunoglobulin was achieved in saline, serum,
of insulin, a patient would use a ball point-pen- and whole blood in10-30 min.

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 International Journal on Current Trends in Drug Development & Industrial Pharmacy
5 Vol 2, Issue 2 - 2017

An alternative approach pursued by Triton Bio- explored by Leong’s group at Johns Hopkins
Systems is to bond iron nanoparticles and School of Medicine [12] as tissue-targeted
monoclonal antibodies into nanobioprobes about carriers for gene delivery into cells that “can
40nanometers long. The chemically inert probes simultaneously bind compacted DNA plasmids
are injected and circulate inside the body, and targeting ligands in a spatially defined
whereupon the antibodies selectively bind to manner” and allow “precise control of
tumor cell membranes. Once the tumor (whether composition, size and multi functionality of the
visible or micro metastases) is covered with gene-delivery system.” The nanorods are electro
bioprobes after several hours, a magnetic field deposited into the cylindrical 100 nm diameter
generated from a portable alternating magnetic pores of an alumina membrane, joining a 100 nm
field machine (similar to a miniaturized MRI length gold segment and a 100 nm length nickel
machine) heats the iron particles tomore than segment. After the alumina template is etched
170 degrees, killing the tumor cells in a few away, the nanorods are functionalized by
seconds. Once the cells are destroyed, the body’s attaching DNA plasmids to the nickel segments
excretion system removes cellular residue and and transfer in, a cell-targeting protein, to the
nanoparticlesa like. Test subjects feel no pain gold segments, using molecular linkages that
from the heat generated. Triton Biosystems plans selectively bind to only one metal and thus
to start designing human tests and ask the FDA impart biofunctionality to the nanorods in a
for permission to begin human clinical trialsin spatially defined manner. Targeted radio immune
2006. therapeutic agents [13] include the FDA-
approved “cancer smart bombs” that deliver
TARGETED NANOPARTICLESANDSMART tumor killingradio active yttrium (Zevalin) or
DRUGS iodine (Bexxar) attached to a lymphoma-targeted
(anti-CD20) antibody.
Multi-segment gold/nickel nanorods are being

Figure 4.Type of nanoparticulate drug delivery systems

Other antibody-linked agents [14] are being tospecifically kill leukemia, lymphoma, breast,
investigated such as the alpha-emitting actinium- ovarian, neuroblastoma, and prostate cancer cells
based “nanogenerator” molecules that use at becquerel (picocurie)levels with promising
internalizing monoclonal antibodies to penetrate preliminary results against advanced ovarian
the cell and have been shown, in vitro, cancer in mice [15].

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Nanomedicine and Nanotechnology: The Future of Pharmacy
Suraj KP et al. 6

Figure 5.Nanogenerators against advanced ovarian cancer in mice

However, drug specificity is still no better than prodrug.” A further improvement in enzyme-
the targeting accuracy of the chosen antibody, activated drugs are “smart drugs” [17] that
and there is significant mistargeting, leading to become medically active only in specific
unwanted side effects. Enzyme-activated drugs, circumstances and in an inherently localized
first developed in the 1980s and still under active manner. Other stimulus-responsive “smart”
investigation separate the targeting and hydrogels are being studied, including a hydrogel
activation functions or instance an antibody composite membrane co-loaded with insulin and
directed enzyme-triggered prod rug cancer glucose oxidase enzyme that exhibits a twofold
therapy is being developed by researchers at the increase in insulin release rate when immersed in
University of Gottingen in Germany. This targeted glucose solution [18], demonstrating “chemically
drug molecule turns lethal only when it reaches stimulated controlled release”.
cancer cells while remaining harmless inside
healthy cells. In tests, mice previously implanted THE PROSPECT OF NANOMEDICINE
with human tumors are given an activating From this simple analogy of body-and-mind to
targeted enzyme that sticks only to human tumor car-and-driver, it might at first appear that the
cells, mostly ignoring healthy mouse cells. The advent of nanomedical technology will confirm
antitumor molecule is injected. In its activated and strengthen the traditional dualist conception
state, this fungal-derived antibiotic molecule is a of the body. But closer inspection reveals that the
highly-strained ring of three carbon atoms that is analogy is at best incomplete, and at worst
apt to burst open, becoming a reactive molecule deeply flawed. This is because mind, first being
that wreaks havoc among the nucleic acid necessarily embedded in physical structure and
molecules essential for normal cell function. But relying upon that structure for its faithful
the molecule is injected as a prodrug–an execution, and second, this physical structure
antibiotic lacking the strained ring and with a now being manipulated at the molecular level,
sugar safety-catch. Once the sugar is clipped off enters also into the purview of our mechanic.
by the previously positioned targeted enzyme, Both car and driver may be modified in the shop.
the drug moleculere arranges itself into a three- Speaking allegorically, it is as if the driver, after
atom ring, becoming lethally active. Notes getting his car a tune-up, emerges from the shop
chemist Philip Ball.16 “The selectivity of the no longer favoring chocolate but enjoying vanilla
damage still depends on antibody’s ability to instead, or now preferring jazz over classical, the
hook onto the right cells, and on the absence of opposite of before. Such psychological changes
other enzymes in the body that also activate the may be either volitional or emergent. Until the

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 International Journal on Current Trends in Drug Development & Industrial Pharmacy
7 Vol 2, Issue 2 - 2017

late 20th century, human progress was measured medical technology. The physical human body
almost exclusively in terms of externalities. Food may be one of the last bastions of “naturalness”.
was gathered then manufactured. Shelters had It will also be one of the last elements in our
no running water, then gained outhouses, then common worldview to be modernized. Our
indoor plumbing. Natural lighting and campfires subjective experience of reality will shift by subtle
gave way to candles, then oil lamps, then electric degrees.
illumination. Finger-counting yielded first to the
abacus, then the mechanical adding machine, and For instance, all objective information about our
finally to the digital computer. But throughout all physical surroundings has traditionally arrived in
of history, the human body itself has remained the conscious mind via the various natural senses
such as hearing, sight, and smell. In the
largely untouched by progress.
nanomedical era, machine-mediated sensory
We have always regarded our bodies, evolved by modalities may permit direct perception of
natural selection, as fundamentally inviolate and physical phenomena well removed from our
immutable subject perhaps to various natural or bodies in both time and space, or which are
traumatic degradations, but rarely to any qualitatively or quantitatively inaccessible to our
significant intrinsic improvement on the original natural senses. Perception will gradually
timescale of human civilization. Now we are set expand to incorporate nonphysical phenomena
to embark upon an era in which our natural including abstract models of mental software,
physiological equipment may for the first time in purely artificial constructs of simulated or
history become capable of being altered, enhanced realities and even the mental states of
improved, augmented, or rendered more others. Such new perceptions will inevitably alter
comfortable or convenient, due to advances in the way our minds process information.

Figure 6.Prospect of Nanomedicine

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Nanomedicine and Nanotechnology: The Future of Pharmacy
Suraj KP et al. 8

NANOROBOTICS encountered by conventional parts. Since these

nano scale devices have not yet been fabricated,
The nanorobots are invisible to naked eye, which evaluating possible designs and control
makes them hard to manipulate and work with. algorithms requires using theoretical estimates
Techniques like Scanning Electron Microscopy
and virtual interfaces/environments. Such
(SEM) and Atomic Force Microscopy (AFM) are interfaces/simulations can operate at various
being employed to establish a visual and haptic levels of detail to trade-off physical accuracy,
interface to enable us to sense the molecular computational cost, number of components and
structure of these nano scaled devices. Virtual the time over which the simulation follows the
Reality (VR) techniques are currently being nano-object behaviors. They can enable nano-
explored in nano-science and bio-technology
scientists to extend their eyes and hands into the
research as a way to enhance the operator’s
nano-world and also enable new types of
perception (vision and haptics) by approaching exploration and whole new classes of
more or less a state of ‘full immersion’ or experiments in the biological and physical
‘telepresence’. The development of nanorobots sciences. VR simulations can also be used to
or nano machine components presents difficult develop virtual assemblies of nano and bio-nano
fabrication and control challenges. Such devices components into mobile linkages and predict
will operate in microenvironments whose
their performance [19].
physical properties differ from those

Figure 7.Nanorobotics with their components

Nanorobots with completely artificial machines continues to increase, we now see a

components have not been realized yet. The possibility of using the natural machines, or
active area of research in this field is focused creating synthetic ones from scratch, using
more on molecular robots, which are thoroughly nature’s components. This chapter focuses more
inspired by nature’s way of doing things at nano on molecular machines and explores various
scale. Mother Nature has her own set of designs and research prevalent in this field. The
molecular machines that have been working for main goal in the field of molecular machines is to
centuries, and have been optimized for use various biological elements - whose function
performance and design over the ages. As our at the cellular level creates motion, force or a
knowledge and understanding of these numerous signal-as machine components. These

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 International Journal on Current Trends in Drug Development & Industrial Pharmacy
9 Vol 2, Issue 2 - 2017

components perform their preprogrammed orientation they would form nano devices with
biological function in response to the specific multiple degrees of freedom, able to apply forces
physiochemical stimuli but in an artificial setting. and manipulate objects in the nanoscale world.
In this way proteins and DNA could act as motors, The advantage of using nature's machine
mechanical joints, transmission elements, or components is that they are highly efficient and
sensors. If all these different components were reliable.
assembled together in the proper proportion and

Figure 8.Bio nanorobotics- a truly multidisciplinary field

Nanorobotics is a field which calls for GOLD NANOPARTICLES

collaborative efforts between physicists,
chemists, biologists, computer scientists, Gold nanoparticle materials are currently being
engineers and other specialists to work towards investigated aspromising agents for medical
this common objective.(Figure 8) details the imaging [21] and therapeutics. Oversea trials
have been conducted with informed consent and
various fields which come under the field of bio
nanorobotics (this is just a representative figure regulatory approval in 4 patients with head and
neck tumor at4.5 mL/kg of 100 optical density
and not exhaustive in nature) [20].
(OD) solution (21 mg/kgnanoshells infused).
Currently this field is still evolving, but several Subsequent patients (4 head and neck,19
substantial steps have been taken by great prostate) have been dosed at 7.5 mL/kg of 100
researchers all over the world and are OD solution(35 mg/kg nanoshells infused). No
contributing to this ever challenging and exciting adverse effects related to device exposure have
field. been seen.

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Nanomedicine and Nanotechnology: The Future of Pharmacy
Suraj KP et al. 10

DIFFERENT TYPE GOLD NANOPARTICLES

Figure 9.Types of gold nanoparticles

The unique physical and electromagnetic dependent upon the placement of the energy
properties of gold nanoparticles, including ease applicator. In contrast, nanoparticle-based
of functionalization, control of size and shape, ablation attempts to use an exogenous material,
optical resonance, and relative inertness of gold the nanoparticle, to transduce the energy and
in the body, allow for a multitude of potential direct the ablation. In these nanoparticle-based
applications ranging from diagnostic imaging, therapies, the objective is to provide a more
drug delivery vectors [22] and exogenous specific ablation of the tumor and spare normal
absorbers for thermal ablation of tumors. One of tissue.
the most promising gold nanoparticle for medical
applications, gold nanoshells, is currently being MATERIALS AND METHODS
used in clinical investigations of the ablation of MANUFACTURING AND CHARACTERI-
solid tumors in head and neck and prostate ZATION OF GOLD NANOPARTICLES
cancers. Gold nanoshells are solid spherical
particles, approximately 155 nm in diameter, with Nanoshells were fabricated under clean
a layer of 5000 molecular weight polyethylene conditions in a class 1000 clean room. Nanoshell
glycol (PEG) covalently bound to the surface to fabrication was based on the method of
increase circulation time in the blood [23-24].The Oldenburg et al.[26] Briefly, gold colloids 1 to 3
spherical particle has an approximately120 nm nm in diameter were prepared using the method
core of silica upon which a thin gold shell has of Duff and Baiker [27]. Aminated spherical silica
been deposited. This dielectric core/metal shell particles 120 + 12 nm in diameter (Precision
structure determines the optical extinction Colloids, LLC, Cartersville, CA) were exposed to
properties of the particle, which is principally at the gold colloid solution forming gold colloid
near infrared (NIR) wavelengths [25]. The spheres nucleation sites on the silica core. The gold seed
are metabolically inert and thus evaluated as sites were then further reacted with hydrogen
medical devices. Traditional energy-based tissue tetrachloroaurate (HAuCl4) in the presence of
ablation techniques (high powered lasers, formaldehyde. This caused the surface colloid to
radiofrequency, microwave, focused ultrasound) grow and coalesce, ultimately forming a complete
rely upon the transduction of the energy source metalshell. Finished particles possessed a 12- to
by the natural components of human tissue, and 15-nm-thick shell that resulted in an optical
there is little discrimination between normal and absorption peak between 780 and 800 nm.
tumored tissue. Accordingly, tumor ablation is Thiolated PEG (SH-PEG; Laysan Bio, Arab, AL) was

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 International Journal on Current Trends in Drug Development & Industrial Pharmacy
11 Vol 2, Issue 2 - 2017

then assembled onto nanoshell surfaces by the 100 OD solution was measured using neutron
combining 1 mmol/L SH-PEG and nanoshells in a activation analysis (NAA) to assess the amount of
ratio of 1.5 mL/mL in deionizedH2O for 12 hours gold in the solution.41Particle size and size
followed by diafiltration to remove the excessSH- distribution were measured using transmission
PEG. Particles were then suspended in 10% electron microscopy (TEM)and dynamic light
trehalose solution\ to create an iso-osmotic scattering (DLS) using a Malvern ZetaSizer
solution for injection and concentrated by (Malvern Instruments Ltd., Worcestershire, UK).
tangential flow filtration to an extinction of 100 + The presence of bacterial endotoxin was
5OD (at 800 nm) to reduce the infused fluid determined by Pyrogent 80 gel clot assay(0.0625
volume. The nanoshellsolution was passed EU/mL sensitivity; Lonza, Allendale, NJ).
through a 0.45-nm filter and filledinto iv bags. For Osmolarity ofthe final solution was measured
the rat and canine in vivo studies, the nanoshell using a Vapro vapor pressureosmometer
solution was terminally sterilized by e-beam (Wescor, Logan, UT).
irradiation. The concentration of nano shells in

Figure 10:A.Illustration of the nanoshell particle geometry B. Representative TEM of PEGylated silica gold
nanoparticle and particle sizedistribution as measured by TEM

REQUIRED RESEARCH INFRASTRUCTURE In fact, a few technological/ clinical centres will

have to specialise on the transfer of nanomedical
Nanomedicine is a very special area of systems from the bench to the patient's bed-the
nanotechnology, because: It is an extremely large “clinicalisation” of the nanomedical devices-to
field ranging from in vivo and in vitro diagnostics take into account its specificities. Testing
to therapy including targeted delivery and patient's bio-samples on nanobio-analytical
regenerative medicine. It has to interface systems, implanting an in vivo nanobio device or
nanomaterials (surfaces, particles, etc.) or injecting a nano - tech based drug carrier require
analytical instruments with “living” human a specific environment in dedicated clinics as
material (cells, tissue, body fluids). close as possible to nanotechnology centres,
“Nanotechnologies in cancer”. Each centre or which is not currently found in the usual
node should already have: excellence in one area university hospitals. These places will also be key
of nano-technology (surfaces, particles, analytics, support facilities for joint training of medical
integrated systems, etc.), a biological and/or doctors and technology developers. Upgrading
medical research centre and hospital, and (most and combining these places therefore is crucial
importantly) companies, which have access to for effective market oriented envelopments in
and knowledge of the relevant markets. Nano biotechnology, because speed is the most

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Nanomedicine and Nanotechnology: The Future of Pharmacy
Suraj KP et al. 12

critical key factor of success for bringing nano require more extensive work. However, this
medical devices or methods to the market in a should not delay patients' access to innovative
competitive situation. medicines since there are procedures in place for
guiding the applicants from the early stages of
EDUCATION AND TRAININGS REQUIRED the development of their products even in
absence of specific guidelines. A need for
Due to its novelty, no dedicated education
improved collaboration between regulators
programme in Nanomedicine exists in Europe at
responsible for Medical Devices and Medicinal
present, with the exception of a few regional
Products is strongly perceived, as integration of
initiatives. Besides education of students, training
competences might be required for complex
of industry and clinical personnel is needed at all
nanotechnology based products.
levels from the nurse to the physicians or the
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 International Journal on Current Trends in Drug Development & Industrial Pharmacy
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