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Nanotube: A New Approach to Novel Drug Delivery System

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Abstract

In present scenario the rise in nanotechnology has marked the greatest move forward in the development of more effective drug delivery systems. The novel nanotechnology has made the target drug delivery system quite easy and effective. Target drug delivery system is a method of delivering the active compound of the medicine to the affected site in the body. Through nanotechnology the transfer of drug is usually in more controlled and apt amount. Nanotubes help transfer the drug to the site of action without interfering with the functioning of non-target cells. This paper discusses the basic outline of what nanotubes are, particularly emphasizing on the carbon nanotubes. In this paper discussion on discovery of nanotubes and structure and functioning of the carbon nanotubes is also done. The recent usage of nanotubes in research of medicine is focused in making target drug delivery systems for therapies like cardiovascular therapy and in making of anti-infectious medicines. These usages of carbon nanotubes are also discussed in the paper.
Nanotube: A New Approach to Novel Drug Delivery
System
Dr. Shashank Tiwari1 & Ms. Shreya Talreja2
1Director, JP College of Pharmacy, Lucknow
2Lecturer, JP College of Pharmacy, Lucknow
Abstract In present scenario the rise in nanotechnology has marked the greatest move forward in the development of more effective
drug delivery systems. The novel nanotechnology has made the target drug delivery system quite easy and effective. Target
drug delivery system is a method of delivering the active compound of the medicine to the affected site in the body. Through
nanotechnology the transfer of drug is usually in more controlled and apt amount. Nanotubes help transfer the drug to the
site of action without interfering with the functioning of non-target cells. This paper discusses the basic outline of what
nanotubes are, particularly emphasizing on the carbon nanotubes. In this paper discussion on discovery of nanotubes and
structure and functioning of the carbon nanotubes is also done. The recent usage of nanotubes in research of medicine is
focused in making target drug delivery systems for therapies like cardiovascular therapy and in making of anti-infectious
medicines. These usages of carbon nanotubes are also discussed in the paper.
Keywords: Nanotubes, carbon nanotubes (CNT), target drug delivery, cardiovascular therapy.
INTRODUCTION
A drug delivery system is defined as an engineered
technology or a formulation that enables targeted delivery
and controlled release of therapeutic agents. It allows
therapeutic agents to reach its site of action selectively
without affecting the non target cells, organs or tissues.
This system is responsible for determining the rate of drug
release in the body and also the site where the drug has to
be released. The various ways of intake of medicines can
be through inhalation, skin absorption, and intravenous
injections or by swallowing them. For every medication
different method of intake can be used as each intake
method has its own merit and demerit. In order to improve
the usage of prevailing medications there is a need for
more efficient and effective drug delivery method either
by improvising the existing ones or by discovering the
new ones. For example, a new method of medicine intake
has been designed which is called ‘micro-needle array ‘it
allows medication to get absorbed through the skin. In the
micro-needle array method, microscopic needles that are
thinner than a hair strand are designed to contain medicine
in them. These deliver the medication in a painless manner
because the needles are so thin and small that they do not
reach the nerves in the skin even though they penetrate the
skin. Another such innovation in drug delivery system is
the invention of the nano-tubes. With the advancement in
the field of biotechnology there is easy availability of
medications that can target diseases more precisely and
accurately. Research has been carried out in order to
design and formulated those drugs which can be used for
specific diseases and health condition. The main purpose
of designing targeted drug is to minimize chance of
commencing dug resistance which is also the concern
when the broad-spectrum antibiotics are used heavily. This
technology has been extensively used in the field of
medicine and is used in manufacture of nano-medicines as
nano particles are of high utility in drug design.
The size of nanoparticles is between 1 and 100 nm. This
technology is highly used in development of nanomedicine
such as nanofluids for drug delivery, biosensors and
microarray tests for tissue engineering. Nanotechnology
has enabled the production of curative agents also.
Nanotechnology has brought significant reforms in the
field of biomedicine by enabling the formation and
discovery of target drug delivery systems and biosensors
etc. Nanoparticles are the spheres of very small size that
are composed of materials designed at the atomic or
molecular level. Due to the small size of nanoparticles
these function at the molecular level. Nanomedicines have
been popularized a lot in today’s time because the
nanoparticles can be utilized as delivery agents by
encapsulating drugs or attaching therapeutic drugs and
delivering them to target tissues in a precise and controlled
manner with the help of these small molecules. A research
study showed that by the use of nanotechnology, the
treatment for certain fatal diseases like glioblastoma and
cancer is also possible. Nanotechnology serves the
purpose of site-specific and target oriented drug delivery
of a particular medicine and hence it proves beneficial for
the treatment of chronic diseases like cancer and
rheumatism. Various nano medicines are available now
which can be used as chemotherapeutic agents, biological
agents and immunotherapeutic agents in the treatment of
various diseases.
Nanotubes: Discovery, characteristics and structure
The discovery of carbon nanotubes was done by Sumio
lijima in 1991. Nanotubes have tremendous physical and
chemical properties in terms of being helpful in making
nano medicine. In the initial phases of nanoparticle-based
therapy, lipids like liposomes and micelles were used. The
liposomes and micelles are good at containing inorganic
nanoparticles like gold etc and are also good at holding
magnetic particles as well. This property of nanoparticles
has enhanced the use of inorganic nanoparticles by
emphasing on drug delivery, imaging and therapeutics
functions. Nanoparticles also helps in preventing
destruction or wastage of medicines in the gastrointestinal
region and also help in the delivery of sparingly water-
soluble drugs to their specific targeted locations.
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1024
Carbon Nanotubes are cylindrical structures made up of
carbon atoms and these are helpful in the process of drug
delivery system. Nanotubes are carbon allotropes which
are generally similar in aspects like thermal and electrical
conductivity, have high mechanical strength and have
good chemical inertness. Hence, these nanostructures play
a crucial role in nanoscience, such as nanomedicine. The
carbon anotubes can be classified in two forms:
(i) Single-walled carbon nanotubes (SWCNs): Single
layer of grapheme constitutes the fundamental
structure of the single-walled carbon Nanotube and
catalyst is also used in this synthesis. High quantity
synthesis of single walled carbon nanotube is difficult
because it also needs properly controlled
environmental factors. These Nanotubes have poor
purity and there are higher chances of defect during
the functionalization. These accumulate less in the
body. The single walled carbon CNTs are highly
malleable and can be easily twisted and molded.
Characterization and evaluation of these is very easy.
(ii) Multiple-walled carbon tubes (MWCNs): These are
made up of multiple graphene layers. These can be
produced without the catalyst and hence their bulk
synthesis is easy. Purity of multi-walled carbon
Nanotube is high and a chance of defect is less but
once occurred it is difficult to improve. These have
more accumulation in the body. It has a very complex
structure and is not very malleable and cannot be
easily modified.
SWCNs contain one single graphite sheet which is
cylindrical in shape. It has a diameter ranging from 0.4 to
3.0 nm. In contrary to this, MWCNs are an array of tubes,
hence named as multi walled. There is a distance between
the layers, and there is significant space between the
graphite layers. The number of layers present in the
MWCNs determines the diameter of the Nanotube. The
inner diameter lies between 0.4 nm to a few nanometers
and the outer diameter lies between 2 to 100 nm. There is
some structural divergence that exists between SWCN and
MWCN which is very distinct. For example, the length of
the tubes of MWCNs has length in micrometer, whereas in
case of SWCN, length is from 1 μm to a few centimeters.
The SWCN have well-defined diameters, whereas in case
of MWCN there are some structural defects, which makes
them relatively less defined in terms of diameters and
inturn structure. Hence MWCN are relatively less stable
materials.
Functionality of Carbon Nanotubes:
In terms of functionality nanotubes have evolved
tremendously since their discovery and have been
contributing greatly in the field of target drug delivery
systems. With the use of carbon nanotubes in the present
drug delivery system, it gives the hope that the new
advancements can be done in this field. Use of CNTs can
prove advantageous over other types of delivery systems
in the following ways:
a) CNTs diminish side effects by targeting agents.
b) It can be used as a carrier of drugs to provide
therapeutic effects.
c) It can work without any side effects and can help
avoid any adverse impact on the immune system.
d) It can be used as a diagnostic agent to monitor certain
parts of the body.
e) It has a capacity of retaining several copies of drugs.
Use of SWCNs was attempted by Heisner et. al. who
formulated triply functionalized SWCNs joined to
doxorubicin as a cure against colon cancer. That system
consisted of carcinoembryonic antigen (a monoclonal
antibody) to identify tumor makers and fluorescein dye to
track nanotubes within cells. After this the application of
this system was done on human colon cancer cells, where
fluorescence visualization via confocal microscopy
showed that SWCNsdoxorubicin conjugate was taken up
by cancerous cells and the release of doxorubicin, SWCNs
remained in the cytoplasmic region of the cancer cells,
while active pharmaceutical ingredients (API) fully
reached the nucleus section where doxorubicin exerted its
effects. This study proves that multiple functionalizations
are beneficial to keep a check on the bioactivity of
pharmaceutical compounds.
Functionalization of the CNTs is very commonly done. It
is done through various techniques such as, covalent
functionalization and non-covalent functionalization.
Functionalisation is the process through which
modification is possible in the nanotubes. Modifications in
nanotubes can help in minimizing cytotoxicity and
increasing biocompability.
Modifications in CNT
1. Covalent Modification:
Through covalent modification it is ensured that more
stable derivatizations can be introduced in various
functional groups on CNTs like halogens, carbenes, and
arynes, etc. This technique facilitates the dispersion of
CNTs because it allows the hydrophilic moieties of carbon
present in the CNTs to ensure joining of these functional
groups. Recently an approach to this is addition of
required molecule through 1,3-dipolar cycloaddition
reactions. In this the condensation of α-amino acids with
an aldehyde results in azomethineylides that are made up
of carbanion neighboring immonium ion. Once the ylides
undergo cycloaddition reactions with dipolarophiles such
as CNTs, they produce pyrrolidine intermediates. This
pyrrolidine intermediate anchores the functional groups on
to CNTs. Another very relevant form of covalent
modifications is the oxidation of CNTs, which generates
oxygen-containing functional groups like carbonyl,
hydroxyl, and carboxylic acids etc. on both tips and defect
sites of the molecule. Carboxylic acids have hydrophilic
character and it allows further attachment of some other
highly hydrophilic residues. Oxygen derivatives being of
poor reactivity they require preactivation either by acyl
chlorides or by a coupling agents such as carbodiimides
and hydroxybenzotriazole. Therefore use of covalent
modification system is still under extensive study and
there are a lot of things yet to be discovered about it.
2.Non- Covalent Modification:
The system of noncovalent modification is more favorable
because such modifications are done through simple
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reactions and conditions like sonication and centrifuge,
and removes the requirement of harsh reaction conditions
and availability of strong reagents. This method of
functionalization poses no threat to the aromaticity of
CNTs and the structural integrity of graphene surface
and tips. The only drawback of noncovalent conjugates is
that they may dissociate from CNTs in biological fluids or
may even undergo exchange with serum proteins. Such a
situation may raise a concern of toxicity. In recent studies
molecules commonly used in noncovalent
functionalizations are surfactants, polymers, and biological
materials such as proteins, nucleic acids, and peptides.
Their attachment to CNTs is physical adsorption on the
outer walls of CNTs; this attachment is due to the van der
Walls forces, ππ, and CHπ interactions. Recent studies
on non-covalent modification of CNTs have revealed that
aromatic compounds are more adequate dispersive agents
because of better ππ interactions. For example, sodium
dodecyl sulfate can disperse CNTs at the concentration of
just 0.1 mg/mL however, since sodium dodecyl benzene
sulfonate (SDBS) bears aromatic residues, it can disperse
CNTs with approximately 10-fold higher concentration. It
can be concluded that the materials mentioned above bind
to CNTs in divergent geometries; while polymeric
materials wrap CNTs to maximize van der Waals
interactions, surfactants form micelle-like assemblies
around graphitic surface. But still extensive research is yet
to happen to study the structures formed by these
associations.
Uptake capacity
Drug loading is defined as a process in which active drugs
are conjugated with the carriers to make them into a final
form of the drug delivery system. CNTs possess a
spherical shape and high surface area to volume ratio,
these have tremendous potential to accommodate drugs.
To increase the loading capacity of the nanotubes, the
hydrophilic and amphiphilic molecules can be attached to
them to do so. This enables the nanomaterials to
pharmaceutical agents through multiple ways, like
encapsulation inside the cavity, attaching on the surface
upon functionalization, and adsorption on the wall or
among the walls of CNTs.
Pros and Cons of using the Carbon Nanotube:
Pros
Cons
It has unique mechanical
properties which offer it
intense in-vivo stability.
These are non-biodegradable,
hence harmful to the
environment in general.
It has extremely large aspect
ratio and can enable mass
production of drug delivery
system on a large scale.
Great variety of carbon
Nanotube makes
standardization and toxicology
evaluation a cumbersome
process.
It is best used for target drug
delivery system and used in
controlled release of drug at
the site where it is needed.
Tissue tolerance and
accumulation in body can be a
cause of toxicity because there
are unknown parameters in it
that require toxicological
profiling of material.
Recent Application of CNT in DDS
In the last twenty years advancement in the
nanotechnology has increased the awareness about utility
of nanotubes in the field of pharmacy and medicine. In the
field of medicine, these materials have been used
extensively as nanovehicles to deliver various active
pharmaceutical ingredient, peptides, proteins, and siRNAs.
Especially functionalized CNTs are highly versatile
systems and are compatible with many routes off
administration. According to studies done on CNTs it is
found that carbon nanotubes are highly effective in
functioning as nano-carriers for the following conditions:
1. Anti-neoplastic
2. Anti- inflammatory
3. Cardiovascular
4. Anti- infection
Anti-neoplastic:
Cancer is one of the most fatal diseases that cause
worldwide death. It is evident through studies that to cure
cancer the actual challenge is to deliver active
pharmaceutical ingredient specifically to the cancerous
region of the human body. Failure to distinguish healthy
tissues results in various side effects such as cardiac or
systemic toxicity and development of resistance to the
active pharmaceutical ingredient. Another challenge is the
multi drug resistance in chemotherapy that has to be
removed during the treatment. In order to survive
antineoplastic agents, tumor cells express P glycoprotein
that pumps the therapeutic agents back outside tissue.
Hence, antineoplastic activity is hindered even before the
drug is given the chance of killing tumorous cells. To curb
these novel technologies of drug delivery systems which
will be potent enough to avaoid such rejection is of
paramount importance. Till now nanoparticles-based drug
delivery system is by far the best remedy to act as a
vehicle for anti-neoplastic medicine to be transferred to
the target tumor. CNTs are utilized to carry antineoplastic
agents, including campthothecin and cisplatin etc. without
causing any distortions in the medicine.
Anti- inflammatory:
The nanotechnology has paved way for advance delivery
of drugs at the areas affected by inflammation and
infection. In order to improve the release profile of
molecules and to improve the cellular intake properties
more research is going on in this field. The area of
stimulated drug release is also under study for curing
inflammation. In this a stimulant triggers the release of the
drug from its carrier. In this process, the nature of
stimulant could range from a molecule like the release of
insulin as a response to glucose or release could be
triggered by physiological conditions like pH or
temperature. These advancements can transform the way
medical science attempts at curing various diseases and
infections including inflammation as well.
Cardiovascular:
Cardiovascular diseases comprise of the diseases that are
related to the heart and the blood vessels. According to
World Health Organization, cardiovascular diseases are
Shashank Tiwari et al /J. Pharm. Sci. & Res. Vol. 12(8), 2020, 1024-1028
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the primary cause of death in the world on a global scale.
Until recently these cardiovascular diseases were cured
with the help of conventional drug delivery system. The
treatment of atherosclerosis and some other cardiovascular
diseases such as cardiomyopathy, rheumatic heart disease,
are restricted by the failure to transport anticardiovascular
medicaments successfully across the endothelium. For
example, rosiglitazone, activates receptor agonist that
helps in curing atheroma by reducing macrophage
infiltration into atherosclerotic lesions. However, some of
its side effects like cytotoxicity and heart failure due to
fluid retention over shadows the pharmaceutical benefits
of this drug. By considering the mentioned side effects of
this drug, there exist the needs for more effective drug
transport systems that are useful in restoring the
therapeutic efficiency of anticardiovascular agents. Other
major reasons due to which there is high dependency on
this novel transport system are:
(1) It improves the solubility of active pharmaceutical
ingredients and increases the bioavailability of the active
molecules in a drug.
(2) It avoids the chances of extreme active pharmaceutical
ingredients loss by the way of urine discharge.
(3) It also improves the physical stability of the active
pharmaceutical ingredients.
In order to deliver anti-cardiovascular agents without
much complication, the following techniques that can be
useful are macromolecular-aided, thiomermediated
approaches, and silica particles. Among these techniques,
the major focus is on the silica particles technique beacuse
any success in drug delivery with this material brings forth
other such techniques like carbon nanotubes (CNTs). With
respect to the findings that silica-based nanomaterials are
feaseable in the delivery of annexin V accelerates the use
of nanomaterials in cardiovascular diseases. Similarly,
CNTs also prove very advantageous in this context due to
their distinct characteristics.
Anti-infective:
Various studies done in the field of medicine show that
infectious diseases are yet one of the major concerns that
needs to be worked upon for the well being of the human
population. The major drawback of any delivery system is
the resistance to the antibiotic against bacteria and the
incapability to formulate newer versions of the antibiotics.
In order to develop insight into it the scientists are doing
elaborate research to study the complications and
applications in drug delivery. The nanotubes are one such
alternative that modern medicine is adopting because since
CNTs are not any antibiotics as such so any medicine
loaded onto them will safely reach the site of action and
the existing bacteria will not be able to make any
resistence towards the inorganic carbon nanotube. This
technology will curb the limitation like most of the anti-
infective APIs are not adequately absorbed by cells
because of their poor solubility and weak cellular
penetration ability, so CNTs will eliminate such problems.
Nanotechnology-based drug delivery approaches, such as
CNTs, are useful in concentrating drugs in pathogenic cell
regions, and hence it will help to cope with bacterial
resistance. CNTs can be indirectly augmented that
enhances the solubility of therapeutic agents, which drug
delivery systems are attached to hence enabling no
wastage of the drug.
CONCLUSION
With the advancement in technology the medicine sector
is highly benefitted as the nanotechnology has enabled the
development of the target drug delivery systems. Through
this paper it can be concluded that the carbon nanotubes
are certainly a very potent method through which
medicine can be subjected to the target area without
affecting the non-target tissues. Carbon nanotubes can be
used in cancer treatment to transfer the chemotherapeutic
drugs only to the affected area. They can be also used in
gene therapy. It can be concluded that nanotechnology has
proven to be a boon to the mankind in terms of advanced
medicine. Though this area of drug delivery system is
highly effective still there is a lot of research yet to be
done in the area of toxicology pertaining to carbon
nanotubes and effective mass production of them.
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... Functionalised CNTs have some beneficial properties in biomedicine and hence CNTs based systems are developed to explore their usefulness in the therapeutic, diagnostic, and analytical applications. Carbon nanotube-based systems have been rigorously investigated in cancer therapy to carry and deliver drugs and to evaluate them for potential lymphatic targeted therapy, gene therapy, thermal therapy and photodynamic therapy [76], [80]- [83]. In addition to their importance in cancer therapy, CNT based systems have been employed for the treatment of genetic disease, fungal infections, neurodegenerative disorders like Alzheimer's disease, and most often as scaffolds for tissue engineering [84]- [86]. ...
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