Nanomedicine: An Emerging Area of Nanotechnology
Ritesh Kumar*, Amit Kumar Jha and Surendra Kumar Jain
ABSTRACT
Nanomedicine is emerging
as the most important discipline under the umbrella of nanotechnology. It is
concerned with the preservation and improvement of human health, using
molecular tools and molecular knowledge of the human body. Simply nanomedicine is the application inside nanotechnology to
the medicine. The pharmaceutical nanotechnology market is concerned especially
with the diagnostic and carrier for drug, which has been rapidly growing over
last decade. Some pharmaceutical nanotechnology based products such as nanoparticles polymer, micelles, dendrimer,
monoclonal antibody and other modified nanosystems
have been approved by US-FDA and have entered in the market. However, some
unknown health risk, unpredictable and undefined safety issues and some
clinical as well as regulatory issues still pose formidable challenge. Thus,
this review justifies the status, scope and importance of nanomedicine
inside the field of nanotechnology.
KEY WORDS: Nanotechnology, Nanomaterials, Nanoscale devices,
Nanomedicine
INTRODUCTION
Nanomedicine is the
process of diagnosing, treating, and preventing disease and traumatic injury,
of relieving pain and of preserving and improving human health, using molecular
tools and molecular knowledge of the human body. Nanomedicine
is an emerging field of medicine with novel applications. Nanomedicine
is a subset of nanotechnology, which uses tiny particles that are more than 10
million times smaller than the human body1. In nanomedicine,
these particles are much smaller than living cell. Because of this, nanomedicine presents many revolutionary opportunities in
the fight of all types of cancer, neurodegenerative disorders and other
diseases. Nanomedicine is beginning to emerge from
research in nanotechnology2. Nanotechnology is the understanding and
control of matter at dimensions of roughly 1 to 100 nanometers, where unique
phenomena enable novel applications3. Encompassing nanoscale science, engineering and technology,
nanotechnology involves imaging, measuring, modeling, and manipulating matter
at this length scale. Nanoparticles are defined as
particulate dispersions or solid particles with a size in the range of 10-1000
nm. The drug is dissolved, entrapped, encapsulated or attached to a
nanoparticle matrix4. The major goals in designing nanoparticles as a delivery system are to control particle
size, surface properties and release of pharmacologically active agents in
order to achieve the site-specific action of the drug at the therapeutically
optimal rate and dose regimen5,6.
Advantages of Nanoparticles
over Nanomedicine
Increased
bioavailability, dose proportionality, decrease toxicity, stable dose forms of
drugs which are either unstable or have unacceptably low bioavailability in
non–nanoparticle dosages forms are the ideal feature of the nanoparticle over nanomedicine. Increased surface area results in a faster
dissolution of the active agent in an aqueous environment. Faster dissolution
generally equates with greater bioavailability, smaller drug doses, less
toxicity, reduction in fed /fasted variability7.
Nanotechnology (Nanomaterials and Nanoscale
devices) for diagnosis, treatment and monitoring diseases is a fast developing
area of biomedical research. It is an amalgamation of engineering science with
pharmaceutical and medical sciences. Nanotech based drug delivery is less toxic
as well as inexpensive. Nanomedicine has a limited
number of current applications. Academic centers including CalTech
and Harvard are using nanowires to create biosensors
capable of identifying proteins in a cells as well as viruses in the hopes of
developing a new generation of diagnostics.
|
S.N. |
Areas of Nanomedicine |
Applications in
Health Care System |
|
1 |
Biopharmaceutics |
Drug delivery Drug encapsulation Functional drug
carrier Drug discovery |
|
2 |
Implantable material
Tissue repair and
replacement |
Implant
coating Tissue
regeneration scaffolds |
|
3 |
Structural implant
material |
Bone repair Bioresorable material
smart material |
|
4 |
Implant device Sensory aids |
Implantable sensor Implantable medical
device Retina implant Cochlear implant |
|
5 |
Surgical aids Operating tools |
Smart instrument Surgical robots |
|
6 |
Diagnostic tools Genetic testing |
Ultra sensitive
labeling and detecting technologies High throughout
arrays |
|
7 |
Imaging |
Nanoparticle labels Imaging device |
Nanotechnology is
suited for better drugs delivery to small regions within the human body as such
drugs can easily cross biological membrane8. Liposomes
are effective for drug targeting by chemotherapeutic agents. The concept of
Nanotechnology helps in optimizing a therapy for glioblastoma, the most malignant of brain cancers.
As a diagnostic tools, efforts of
nanoparticle is directed on utilizing a lab-on-a-chip devices to perform DNA
analysis and drug discovery research by reducing the required sample sizes and
accelerating the chemical reaction process9. Moreover, imaging
technologies such as nanoparticle probes and miniature the imaging devices that
could promote early detection and diagnosis of disease.
Some examples of
application of nanotechnology are:
1.
Intracellular drugs delivery through
spontaneously forming nanotubes.
2.
Lipid complexes for i.v.
administration of antifungal.
3.
Submicron triglycerides emulsions for parenteral nutrition.
4.
Accelerated wound healing because of silver
nanoparticle antimicrobials as dressings.
Nanocrystals based
drugs are Rapamune (sirolimus),
Emend (aprepitant), TriCor
(fenofibrate).
The Nanotechnology act for understanding basic life
processes
on using nanoscale devices and materials to learn
more about how biological systems self-assemble, self-regulate, and self
destroy at the molecular level. Drug delivery is one of the most
promising fields of nanotechnology11,12.
Medical Nanomaterials
and Devices that Signify Nanomedicine
a) Dendrimers and Dendrimer -
Based Devices
Dendrimers represent yet another
nanostructured material that may soon find its way
into medical therapeutics13. Starburst dendrimers
are tree-shaped synthetic molecules with a regular branching structure
emanating outward from core that form nanomer by
nanometer, with the number of synthetic steps or “generations” dictating the
exact size of the particles, typically a few nanometers in spheroid diameter.
The cell-surface protein recognition-targeting strategy could be applied
against virus-infected cells and parasites. Molecular modeling has been used to
determine optimal dendrimer surface modifications for
the function of tecto-dendrimer nanodevices
and to suggest surface modifications that improve targeting14. Dendrimer represents a new class of controlled structure
polymer with nanometric dimensions. They are
considered to be basic element for large-scale synthesis of organic and
inorganic nanostructure with dimension of 1 to 100 nm, displaying unique
properties15.
Table 2. Nanoparticles with their
b) Magnetic Nanoparticle and Immunoassay
It label
the choices so that its interaction with the analyze gives magnetic signals
tube used instead of an optical one magnetic nanoparticles.
Its detection is possible only by magnetometer. The advantage attributes for
detection of subunits modification is in magnetic characters, ability to detect
circulation cancer cells and
microorganism16,17.
c)
Nanobarcodes
The
sequential electrochemical deposition of metal ions to give sub micrometer
metallic barcodes whose differential relativity can lead to identification of
the unique striping patterns by light microscope. Basically it is used for
multiplexed protein assay and single nucleotide variation mapping does not
interfere with the use of fluorescent labeling18.
Table 3.
Different Parameters and Characterization of Nanoparticles
|
S.N. |
Parameters |
Characterization
Method |
|
1 |
Particle
Size & Size distribution |
Photon
correlation spectoroscopy, Scanning
electron microscopy (SEM), Transmission
electron microscopy (TEM), Atomic force microscopy (AFM), Mercury porositometry, Laser defractometry |
|
2 |
Charge
Determination |
Laser
droplet anemometry, Zeta potential |
|
3 |
Surface
Hydrophobicity |
Water
contact angle measurement, Rose bangle (dye) binding, hydrophobic interaction
chromatography, X-ray photoelectron spectroscopy |
|
4 |
Chemical
Analysis of Surface |
Static
secondary ion mass spectrometry, Sorptometer |
|
5 |
Carrier
Drug Interaction |
Differential
scanning calorimetry |
|
6 |
Nanoparticle
dispersion stability |
Critical
flocculation temperature |
d)
Nanowires
It is
similar to the other nanoparticle e.g. gold and QDS but are characterizes by
different shapes thus allowing for different interaction with different
entities and ore unique optimal signals. It can associated with the almost any
chemical or biological recoginization system which allow real time detection
analyst independent ,that can be
conjugated with the almost any bimolecular recoginization
entity suitable for the use in vivo diagnostics19. Nanowires are
semiconductive or semiconductive
particles with a crystalline structure of a few dozen nm and a high
length/diameter ratio. Silicon, cobalt, gold or copper based nanowires have already been produced. They are used to
transport electrons in nanoelectronics. It could be
composed of different metals, oxides, sulphides and
nitrides20.
e)
Nanopores
The pores
of definite size in the nanoscale range on membrane
between two solutions on application of
current, the pores allow only nucleic acids or charged biomolecules
or particular size to pass, further these are than directly translated into
electric signals on the passage through the pore. Its act as a label less
immunoassay for flow system as sensitive enough to detect single base
substitution in DNA strands or the length of 30 nucleotides21.
f) Nanocapacitor
It acts
with the electrode spacing in the nanoorder with
single stranded DNA pores; target hybridization produces a measurable change in
capacitance. Its array allow for label less simultaneous detection or nucleic
acids22.
g)
Nanotubes
The array
of Nanotubes e.g. carbon or boron nitride are used
electrode with single stranded DNA probes attached to their open end,
hybridization or target DNA gives an electrochemical signals, they can also be
adapted for analyst other than DNA. The detection technique is sensitivity in
the attomole range and reduction of signals to noise
radiation and minimize the need for amplification of target DNA23.
h)
NanoBiosensors
Based on
high specificity of biological reactions for detecting target analyzes,
biosensors, which are useful research tools to discover genetic abnormalities
and physiological disease. Biosensors couple is a biological recognition
element with a physical transducer that translates the bio-recognition event
into a measurable effect, such as electrical signal, an optical emission or a
mechanical motion. A new class of promising nanobio-sensor
to detect bimolecular interaction with great accuracy is the microcantilever. This new class of highly sensitivity
biosensors can perform local, high resolution and label-free molecular
recognition measurement. Mechanisms of these biosensors are based on cantilever
in atomic force microscopy (AFM) 24.
The concept
of Nanodiagnostics arises the fact that most
biological molecules and cell organelles fall within the nanometer scale. For
example, the typical protein has a size of 5 nm. The Nanoparticles
used for detection can be synthesized to be within this same size domain19,25.
Current diagnostic methods measure or determine a particular property as an
average of the individual contributions of an ensemble of units or particles.
Thus, such methods do not convey any information about the individual members
in a heterogeneous population or about the lifespan of the various members
within the population26.
Characterization
of NanoParticles
The nanoparticles are generally characterized for the particle
size, charge determination and surface hydrophobicity.
Different parameter and characterization methods for nanoparticles
are summarized on the given table 327
Expectation
from Nanomedicines
Nanotechnology is the
beginning to change the scale and methods of vascular imaging and drug
delivery. Nanomedicne initiative envisages that nanoscale technologies will begin yielding more miracle
benefit within the next 10 years28-31. This includes the
development of nanoscale laboratory based diagnostic
and drug discovery platform devices such as nanoscale
cantilevers for chemical force microscope, microchip devices, and nanopore sequencing32. The Asia-Pacific Economic
Cooperation (APEC) Center for Technology Foresight predicts the development of
selective nanosensors and drug delivery systems over
the next three years, and the application of advanced medical diagnostics and
the ability to target human cells for organ repair by 201333. The
range of long-term expectations in nanomedicine
expands from more cautious forecasts into a realm. Some scientists view as
science fiction nanomedicine, which could potentially
overthrow traditional notions about disease and health to user in a form of
medicine based on prediction and prevention instead of treatment34.
In future the field of nanomedicine will become
particularly relevant due to the increasing politicization of the
nanotechnology debate, and subsequent calls for new regulations by
non-governmental organizations. Hence by generating new ideas the expectation
of nanomedicine inside the public health sector could
uplift inorder to change the life style of the
healthy person. By the use of various drug delivery devices it offers direct on
site drug delivery effect and provide direct release, and thus increase patient
acceptabilty35.
CONCLUSION
Nanomedicine posses a bright
future as if it is the hope that in the first half of the 21st century, nanomedicine
could eliminate virtually all common diseases of the 20th century,
and virtually all medical pain and suffering as well. The sort of materials
that could be called nanomedicines can include
proteins, polymers, dendrimers, micelles, liposomes, emulsions, nanoparticles
and nanocapsules. This technology is expected to
create innovations and play a vital role in various biomedical applications not
only in drug delivery and gene therapy, but also in molecular imaging,
biomarkers and biosensors. However as nanomedicine
becomes a global movement, it is paramount that the hype be separated from
reality. In addition, societal, environmental and ethical concerns will also
need to be addressed as breakthroughs in nanomedicne
as a source to cure human health.
REFERENCES
1.
Freitas RA. Current
status of nanomedicine and medical nanorobotics. J.Computational and
Theoretical Nanoscience. 2005; 2: 1-25.
2.
Langer R. Biomaterials in drug delivery and
tissue engineering: One laboratory's experience. Acc Chem. Res. 2000; 33:
94-101.
3.
Bhadra D. et al. Pegnology: A review of PEG-ylated
systems. Pharmazie. 2002; 57: 5-29.
4.
Vila A. et al. Design of biodegradable
particle for protein delivery. J. Control Release. 2002; 78: 15-24.
5.
Mu L and Feng SS. A
novel controlled release formulation for the anticancer drug paclitaxel (Taxol(R)): PLGA nanoparticles containing
vitamin E TPGS. J Control Rel. 2003; 86: 33-48.
6.
Roco MC.
Government nanotechnology funding: An International Outlook. J. of the
Minerals, Metals and Materials Society. 2002; 54(9): 22-23.
7.
Tefft EP and Simkin MM. Application of nanotechnology: A case study in
pharmaceutical arena (online). Foley and Lardner LLP. Available from: http://www.foley.com/files/tbl_s31Publications/FileUpload137/2007/1180354
1.pdf.
8.
Festinesi A. et
al. Human glioblastoma
cells for gadolinium neutron capture therapy.Cancer
Res. 2001; 61: 4272-4277.
9.
Nanotechnology Enabling Lab-on-a-Chip
Devices.
10.
David A. et al. Nanomedicine
for respiratory diseases. European Journal of Pharmacology. 2006; 33: 341-350.
11.
Tegart G. and Sripsipan. The technology for the 21st century.
12.
Kim GJ. et al. Nanotechnology in cancer
therapeutics: Bioconjugated nanoparticles
for drug delivery. Mol.Cancer Ther.
2006; 5: 1909-17.
13.
Bielinska AU. et al.
Proc. Natl. Acad. Sci. (
14.
Bielinska AU. et al.
J. Pharm. Sci. Technol. 2002; 3: 232.
15.
Quintana A. et al. J. Parma. Res.2002; 19:
1310.
16.
Tomalia DA. Birth
of a new macromolecular architecture: Dendrimer as
quantized building blocks for nanosclae synthetic
organic chemistry. Aldrichimica Acta.
2004; 37: 39-57.
17.
Jain KK. Nanotechnology in clinical
laboratory diagnostics. Clin Chim
Acta. 2005;358: 37-54.
18.
Jain KK. Nanodiagnostics:
application of nanotechnology in molecular diagnostics.Expert
Rev Mol Diagn. 2003; 3:153-156.
19.
Freeman RG et al. Sub micrometer metallic
barcodes. 2001; 294:137–41.
20.
Salata O.
Applications of nanoparticles in biology and
medicine. J. Nanobiotech.2004; 2: 3-5.
21. Fortina P. et al. Nanobiotechnology: the promise and reality of new
approaches to molecular recognition. Trends Biotechnol.
2005; 23: 168–73.
22. Carrascosa LG. et al. Nanomechanical biosensors: A new sensing tool TrAC Trends in analytical chemistry. 2006; 25:
196-206.
23.
Susan A.
24.
Cui Y. et al. Multiplexed electrical
detection of cancer markers with nanowire sensor
arrays. Nat Biotechnol. 2005; 23: 1294–1301.
25.
26.
Vyas SP and Khar RK. Nanoparicle. In: Targeted and controlled drug Delivery
system, CBS publication, 2002; 356-361.
27.
Tyagi S and
Kramer FR. Molecular beacons: Probes that fluorescence upon hybridization
.Nat.Biotechnol.2001; 14: 303-308.
28.
Taton TA, Lu G
and Mirkin
29.
Perez JM, Josephson L and Weissleder
R. Use of magnetic nanoparticle as nanosensors to probe for molecular interactions. ChemBioChem.
2004; 5: 261-264.
30.
Saleh A. etal. In vitro MRI of brain inflammation in Human ischaemic stroke. Brain.127: 1670-1677.
31.
Dousset etal. Comparison of ultrasmall
particles of iron oxide (USIOP) enhanced T2 Weighed, conventional T2 weighted,
and gadolinium –enhanced T1 weighed MRimages in
rats with experimental autoimmune encephalomethylitis. Am. J. Neuroradial
.1999; 20: 223-227.
32.
Lavan D.A. and
Langer R. Moving smaller in drug discovery and delivery. Nat Rev Drug Discov. 2002; 1: 77-84.
33.
Weiss S. Fluorescence spectroscopy for single
biomolecules Science 1999; 283:167683
34.
Emerging nanomedicine
technologies could dramatically transform medical science
NewsMedical.net.July23, 2004
Accessedonlineathttp://www.newsmedical.net/?id=3543.
35.
Scamehorn J.F.,
Phenomena in Mixed Surfactant Systems, American Chemical Society,
Received on
01.05.2009
Accepted on
14.06.2009
© A&V
Publication all right reserved
Research
Journal . of Pharmaceutical Dosage Forms and Technology. 1(1): July.-Aug. 2009, 18-21