Carbon Nanomaterial As a Nanosyringe: A NearFuture Reality

24. Carbon Nanomaterial As a Nanosyringe: A NearFuture Reality

24.1. Introduction
The application of nanotechnology has tremendous potential in health care,
particularly for the development of better pharmaceuticals. Nanotechnologyenabled drug delivery has already been successful in delivering drugs to
specic tissues within the body, with the promise of capability that will
enhance drug penetration into cells, as well as other means to improve drug
activity. It is known that the ecacy of a drug can be increased if it is
delivered to its target selectively and if its release prole is controlled.
In the past decade, two blossoming technologies have been hot research
topics internationally. The powerful utility of concerted application of
nanotechnology and biotechnology has been recently exemplied by
breakthroughs in bio-directed nanosynthesis, nanoassembly, and nano-aided
biologic recognition. Eorts are currently focused on searching for methods
to mimic or exploit the unique capabilities of bioagents in producing
nanostructures.
Nanodevices have shown capability in performing clinical functions such as
detecting cancer at its earliest stages, pinpointing cancers location in the
body, and delivering anticancer drugs specically to malignant cells.
Nanoscale devices can control the spatial and temporal release of
therapeutic agents or drugs. Nanoscale devices are much smaller than cells
and even many cell organelles. Most animal cells are 10,000 to 20,000 nm in

diameter. This means that nanoscale devices smaller than 50 nm can easily
enter most cells, and those smaller than 20 nm can transit out of blood
vessels. As a result, nanoscale devices can readily interact with biomolecules
on both the cell surfaces and within the cells. Hence, a nanoscale device may
contribute to cancer therapy by being a drug carrier.
Nanoscale devices attached with antibodies and loaded with drugs can serve
as a targeted drug-delivery vehicle that can transport chemotherapeutics or
even therapeutic genes into diseased cells while sparing the loading of
healthy cells with drugs. Targeting a drug to its site of action would not only
improve the therapeutic ecacy but also enable a reduction in the total dose
of the drug that must be administered to achieve a therapeutic response,
thus minimizing unwanted toxic eects of the drugs. Dendrimers, silicacoated micelles, ceramic nanoparticles, and cross-linked liposomes have
already been shown to have potential as drug carriers. Moreover, carbon
nanomaterials (CNMs) that have been extensively used for various
bioapplications also show the possibility of being used for drug delivery
(Parihar et al., 2006).
One of the primary objectives in the development of a drug-delivery system is
the controlled delivery of drugs to its site of action at an optimal rate
(Kreuter, 1991) and in the most ecient way possible. Nanoparticles, chiey
because of their small particle size, oer many advantages for many medical
applications (Kreuter, 1983b; Marty and Oppenheim, 1977). The particle size
enables intravenous (IV) and intraarterial injection because particles of this
size can easily traverse even the smallest blood capillaries with an inner
diameter of 3 to 8 m (Thews et al., 1999). A small size also minimizes
possible irritant reactions at the injection site (Little and Parkhouse, 1962;
Kreuter, 1994a & b).
Many nanoscientists fantasize that as soon as CNMs are introduced into a
living system along with drugs, they can act as a self-driven syringe and
deliver the medicine to the site of requirement. Scientists are even planning
to make CNM a disposable syringe that can be removed from the system
either by degradation or excreting it from the system. There have been
reports by Wang et al. (2003) about carbon being a cytotoxic material.
Another school of thought believes that CNMs damaging eect on living cells
is exhibited only when they are exposed to light (Sharon et al., 2000). On the
brighter side, researchers from Rice University have found that the toxicity

of water-soluble carbon nanotubes (CNTs) to human skin cells decreased as

the functionalization of the CNTs increased. They have also shown that CNTs
were generally less toxic than fullerenes.

24.2. Denition of Nanoparticles for Pharmaceutical and

Medical Purposes
Nanoparticles for pharmaceutical purposes are dened by Kreuter (1994b) in
the Encyclopedia of Pharmaceutics Technology

as solid colloidal particles

ranging in size from 11000 nm (1 m). They consist of macromolecular

materials and can be used therapeutically as drug carriers, in which the
active principle (drug or biologically active material) is dissolved, entrapped
or encapsulated, or to which active principle is adsorbed or attached.

24.3. History of the Development of Carbon Nanomaterial

The use of dierent types of nanomaterials for drug delivery was envisaged
more than 4 decades ago. In the late 1960s and early 1970s, Peter
Speiser at ETH (Swiss Federal Institute of Technology, Zurich) realized Paul
Ehrlichs idea and developed the rst nanoparticle for drug-delivery
purposes (Birrenbch and Speiser 1976; Kopf et al., 1976, 1977). These
nanoparticles were produced by emulsion polymerization of acrylamide crosslinked with N,N-methylene bis acrylamide in hexane.
Zolle et al. (1970) used another process, denaturation of albumin dissolved in
water and emulsied in hot cottonseed oil, to produce nanoparticles.

99m TcO

was bound to the nanoparticles, and these particles were used for

radioimaging of the lungs after IV injection. Later, the albumin nanoparticles

were used for drug delivery. Kramer (1974) incorporated the anticancer drug
mercaptopurine into these particles using heat denaturation.
Widder et al. (1978) performed the rst successful drug targeting with
nanoparticles by incorporation of magnetite particles into similar albumin
nanoparticles and the use of a magnetic eld. They substituted a more
ecient anticancer drug, doxorubicin, for mercaptopurine.
The latest important input in the improvement of drug targeting with
nanoparticles is the development of Long circulating nanoparticles by the

covalent linkage of polyethylene glycol (PEG) chains to poly lactic-co-glycolic

acid (PLGA) (Gref et al., 1994) or to poly-alkyl cyanoacrylate nanoparticles
(Peracchia et al., 1998) and delivering the drugs to the brain across the blood
brain barrier (Kreuter et al., 1995).
In 2005, scientists at the University of Trieste, University of Ferrara,
International School for Advanced Studies, and National Consortium of
Material Science and Technology used CNTs to boost neural signaling. They
grew nerve cells from the brains hippocampus region on substrates coated
with networks of CNTs and found a large increase in neural signal transfer
between cells (Lovat et al., 2005). Because CNTs are similar in shape and size
to nerve cells, they could help to structurally and functionally reconnect
injured neurons. Hippocampal neurons grown on CNTs display a sixfold
increase in the frequency of spontaneous postsynaptic currents.
Because CNTs could act as supportive devices for bridging and integrating a
functional neuronal network, scientists have also started viewing carbon as a
possible tool for drug delivery.

24.4. Drug Delivery Promises of Carbon Nanomaterial

To use CNMs for drug delivery, it is important to understand their
morphology and properties. Many characteristics of CNMs are discussed in
detail in previous chapters.
24.4.1. Morphology of Carbon Nanomaterial
Carbon nanoparticles exhibit tubular, brous, and bead-like structures
named CNTs, carbon nanobers (CNFs), and carbon nanobeads
(CNBs), respectively. Although many physical and chemical parameters and
characteristics of CNMs make them a suitable material for drug delivery, so
far they have not been considered seriously, and very few successful results
are available.
24.4.1.1. CARBON NANOTUBES
CNTs are concentric shells of graphite formed by one sheet of conventional
graphite rolled up into a cylindrical form. The lattice of carbon atoms of
graphite sheets remains continuous around the circumference of the CNTs.

Hence, CNTs are fullerene-related structures closed at both ends with caps
containing pentagonal rings. They were discovered in 1991 by the Japanese
electron microscopist Iijima, who was studying the material deposited on the
cathode during the arc-evaporation synthesis of fullerenes. He found that the
central core of the cathodic deposit contained a variety of closed graphitic
structures, including nanoparticles and CNTs, of a type that had never
previously been observed.
CNTs are of two types: single-walled CNTs (SWCNTs) and multi-walled CNTs
(MWCNTs).
In SWCNTs, there are only tubules and no graphitic layers around them. The
diameter of an SWCNT is up to 2 nm, and the length varies as per production
procedures from 3 to 10 m. The arrangement of carbon in an SWCNT can be
of the arm-chair, zigzag, or chiral pattern. SWCNTs are mostly produced in a
bundle and are then separated by chemical or physical methods.
MWCNTs are stacks of graphene sheets rolled up into concentric cylindrical
structures. Their diameter is in the range of 10 to 50 nm, and their length
can be up to or more than 10 m. The individual graphene sheets are
separated by about 0.34 nm.
24.4.1.2. CARBON NANOFIBERS
CNFs are laments without a lumen. They can be produced in various
shapes, including straight, coiled, cactus, cauliower, octopus, stacked, or
sh-bone (herring-bone) shaped.
24.4.1.3. CARBON NANOBEADS
CNBs are spherical, hollow structures. When ve to seven beads are covered
by a broken graphene sheet, the bead is called a spongy bead. The thickness
of each graphene sheet is 8 to 10 nm and the total diameter of the beads is
around 250 to 800 nm.

24.5. Synthesis and Purication of Carbon Nanomaterial

The synthesis, opening, and thinning of SWCNTs, MWCNTs, and
nanomaterials are topics of immense interest owing to their potential

applications in catalysis, nanoelectronic devices, drug delivery, and the

nanoscale chemistry of CNTs (Ajayan, 1999; Harris, 1999; Heer and Martel,
2004; Service, 1998).
For drug delivery, it is important to use highly pure CNMs. Carbon
nanostructures are generally synthesized by three processes: arc discharge,
laser ablation, and catalytic chemical vapor deposition. Details of purication
of synthesized CNMs are given in Chapters 2 to 5.
Synthesis of CNM involves use of catalysts, which often remain along with the
nally produced CNM. To get pure CNM, it is necessary to remove the
catalyst. Moreover, amorphous carbon often also gets synthesized during
CNM production. Hence, during purication, care is taken to remove the
amorphous carbon.
Various purication procedures have been reported in the literature
(Monthioux et al., 2001). Most of them are done by using acids such as HCl or
H 2SO

or other oxidizing reactants such as H 2O 2. These purication

procedures are performed with the main goal of removing the catalyst
particle and impure carbon phases such as amorphous carbon, polyaromatic
shells, and graphite particles.
Removal of catalysts, which are usually metals, is normally done by HCl
treatment; oxidizing acids are used for removal of amorphous carbon
deposits.
Recently, Hirsch and Vostrowsky (2005) proposed a method to obtain a pure
homogenous dispersion of MWCNTs by functionalizing with pyrrolidine
groups to enhance their solubility in the organic solvent dimethyl-formamide,
which is evaporated and then heated at 350C to defunctionalize them in the
process, leaving puried nanotubes on the substrate.
To optimize the structural features of carbon nanostructures for drug
delivery, heat treatment or treatment in activating or passivating gas
atmospheres is done.

24.6. Properties of Carbon Nanotubes

Some important properties of CNTs and their molecular background that may
aect drug delivery include their chemical reactivity, electrical conductivity,

optical activity, and mechanical strength.

24.6.1. Chemical Reactivity
The chemical reactivity of CNTs is usually more than that of the graphene
sheet. CNT reactivity is directly related to s-orbital mismatch caused by an
increased curvature. Therefore, a distinction must be made between the
sidewall and the end caps of CNTs for the same reason. A smaller CNT
diameter results in increased reactivity. A covalent chemical modication of
either the sidewall or end caps is possible.
Although CNMs are usually insoluble material, the solubility of CNTs in
dierent solvents can be controlled or enhanced by creating chemical bonds.
24.6.2. Electrical Conductivity
The electrical conducting properties are caused by the molecular structure.
The conductance is determined by quantum mechanical aspects and was
proven to be independent of the length of the CNTs. However, depending on
their chiral vector (which controls the diameter of the CNTs), CNTs are either
semiconducting or metallic in nature.
24.6.3. Optical Activity
Theoretical studies have revealed that the optical activity of CNT disappears
as the CNTs become larger. It is, therefore, expected that other physical
properties could also be inuenced by the size of the CNTs.
24.6.4. Mechanical Strength
CNTs have very high tensile strength, so they exhibit very large young
modulus in their axial direction. CNTs are also highly exible; therefore, they
are potentially suitable for applications in composite material that need an
isotropic property.
CNMs have diverse tunable physical properties as a function of their size and
shape due to a strong quantum connement eect and large surface-tovolume ratio. CNTs are hollow, tubular, caged molecules Because of these
properties, they have been proposed as lightweight packing material for
hydrocarbon fuels and as nanoscale containers for molecular drug delivery.

24.7. Carbon Nanomaterial for Drug Delivery

The minimum diameters of SWCNTs are similar to the diameter of a molecule
of DNA, so SWCNTs can easily traverse through cells. However, the length of
CNM varies according to the method of production, so it is important that
they are tailored to the right size for drug delivery.
Filling of opened CNTs has already been successfully done with DNA and
proteins. This has given impetus to consider CNM for drug delivery.
Depending on whether the drug is to be adsorbed into the CNM surface or
lled into the lumen of CNTs, the treatment of CNM for drug loading varies.
CNBs have recently attracted attention for use as a drug-carrying vehicle.
The advantage of using CNBs would be that their smaller and desired sizes
can be synthesized by controlling the pyrolysis conditions and the precursor
(Sharon et al., 1998).
Another form of CNM that is also being investigated in our laboratory is
CNFs. As mentioned, CNFs exist in various forms (e.g., straight, coiled, spiral,
branched, bamboo-like, octopus). It has been found that the activation of
CNFs with KOH creates pores on the CNF surface, thus increasing the
available surface area for functionalization or drug attachment, which is a
necessary requirement for drug loading onto CNM.
A detailed survey of the cytotoxicity and degradability of CNM inside living
cells needs to be worked out before attempting the use of CNM for drug
delivery. This is discussed in Chapters 19 and 24.
24.7.1. Steps Involved In the Delivery of Drugs Using Carbon
Nanomaterial
The steps considered for drug delivery are discussed in the next sections.
24.7.1.1. O PENING

THE

CLOSED ENDS

OF

CARBON NANOTUBES

CNT opening has been demonstrated to be a side eect of the various acidbased purication procedures (as mentioned in Sec. 24.5). Oxidative
cleavages of C=C bonds and the presence of greater angular strain due to
geometry (pentagonal rings) are considered to be some of the possible

reasons for initiation of oxidation at the tips or caps (Hwang, 1995), thus
opening the closed ends.
24.7.1.2. CUTTING

OR

TAILORING CARBON NANOMATERIAL

TO THE

DESIRED S IZE

Shorter tubes have found many applications, such as in eld emission,

composites, and medicines. Various approaches have been developed for
either opening or cutting the tubes of both SWCNTs and MWCNTs (Ajayan et
al., 1993; Tsang et al., 1993, 1994). The most common methods are abrasive
treatment and ball milling.
Abrasive Treatment Abrasive treatment is a physiochemical method used
for reducing the length of CNTs. The MWCNTs are dispersed in organic
solvent, and using ultrasound and magnetic stirring at ambient temperature,
they are abrased into smaller segments. The alcohol in the homogeneous
suspension of the CNTs is then evaporated completely. Evaporated ne
carbon powders are smaller in length (Maurin, 2001). However, this method
has its limitations in yield and often creates important structural damage.
Ball Milling Ball milling is a physical method of reducing the length of CNMs
(CNFs and CNTs). Dierent-sized CNMs can be obtained by controlling the
frequency and time of ball milling (Fig. 24-1). The drawback of this method is
that uniform-sized CNMs are not produced, and even the structure of the
CNMs is damaged.
Super Critical Water Treatment Water has unique properties above its
critical point (T c, 374C; P c, 3200 psi), where T
c

is critical temperature and P

is critical pressure. Lowering of the dielectric constant (from 80 at ambient

conditions to less than 5 above the critical point) and reduction of hydrogen
bonds make super critical water (SCW) an ecient nonpolar solvent.
Nonpolar organics are completely soluble in SCW in the presence of oxygen
and could be rapidly and eciently oxidized to carbon dioxide and water in a
single homogeneous uid phase with no interphase mass transfer limitations.
Because the extent of hydrogen bonding in water is lowered under super
critical conditions, it tends to be more reactive.

Figure 24-1. Scanning electron micrograph of carbon nanobers

before (A) and ball milling after (B).
The use of the SCW system for opening and thinning of MWCNTs (Figs. 24-2
and 24-3) has been found to be an easy and rapid method that avoids the use
of strong acids. In addition, it is pollution free.

Figure 24-2. Opening of multiwalled carbon nanotubes in super

critical water in the absence (A) and the presence (B) of oxygen.
(Courtesy of Chang et al., 2002.)

Figure 24-3. Thinning of multiwalled carbon nanotubes by super

critical water in the absence (A) and the presence (B) of oxygen.
(Courtesy of Cheng et al., 2002.)

24.7.1.3. CHEMICAL FUNCTIONALIZATION

OF

CARBON NANOTUBES

Because CNMs are insoluble in both polar and nonpolar solvent, they exhibit
a very low process ability. Chemical functionalization of CNTs has been done
to overcome the problem of process ability.
Several laboratories have investigated the surface chemistry of CNTs,
focusing most frequently on the ends and the outer shell of the CNTs. When
the ends of the CNTs are opened, which is a general consequence of
purication of the as-produced nanotubes, the interior of the nanotubes
becomes ready to accommodate guest materials. The carbon shell is closed
by various functional groups, most frequently by -NH 2, -COOH, -OH, and

>C=O groups (Timea et al., 2004). For MWCNTs, the outer shell often
contains discontinuous spots and imperfections. These local vacancies are
also closed by functional groups mentioned above. However, for these local
applications in which nanotubes are used to strengthen polymers, the
presence of functional groups is advantageous to ensure chemical bonding
between polymers and llers or to enhance the solubility of CNTs in various
solvents.
A team of scientists from Rice University has come up with a new technique
for attaching amino groups to the sidewalls of SWCNT. They have produced
functionalized CNTs by reacting ouronanotubes with terminal diamines.
Attaching the amino functionality to the sidewalls of the tubes provides
multiple sites for creating covalent bonds to monomers or polymers. This
opens up an opportunity for covalent binding of DNA or drugs to the
functionalized tubes.
24.7.1.4. DRUG LOADING
When organic polymers are used as a drug carrier, drugs are incorporated or
loaded during preparation of the polymer. Similarly, there have been reports
of CNMs being loaded with dierent metals during synthesis of CNM
(Seraphin et al., 1993). But drug molecules cannot be loaded in this way
because CNMs are prepared at a very high temperature (i.e., ~750C
onward), which may be damaging the drug molecules to be loaded. Before
loading the drug onto the CNM, a detailed study of the characteristics of
both the drug and the CNM is required.
Drugs may be bound to a nanoparticle by:
Incorporation in to the interiors of a nanocapsule (Soppimath, 2001)
Covalent binding (Kopf et al., 1976; Langer et al., 2000a)
Electrostatic binding (Homann et al., 1997; Langer et al., 1997)
Surface adsorption (Berg et al., 1986; Vora et al., 1993)
In most cases, as per the physicochemical properties of the drug, the method
of drug binding and the type of nanoparticles to be used are decided upon
(e.g., thermolabile drugs cannot be incorporated into a nanoparticle
produced by involving heating). Similarly, hydrophilic drugs cannot be

incorporated into a hydrophobic nanoparticle without diculties and vice

versa. Surface adsorption in general is governed by a Langmuir type of
interaction (Berg et al., 1986; Vora et al., 1993). Surfactants generally reduce
adsorption. In some cases, however, they improve adsorption (Harmia et al.,
1986a & b).
Although loading of a drug onto CNM has not been standardized, methods
that have shown promises in fullerenes and metal insertion can be
considered and tried for drug loading. Some of them are:
1. Collisions of accelerated atoms [with KE (kinetic energy) 150 eV for alkali
metals] on SWCNTs (Farajian et al., 1999), which is used for lling
endofullerenes with metal and other atoms
2. Opened SWCNTs along with the drug to be inserted are taken in glass
ampoule, sealed under vacuum conditions, and then heated beyond the drug
sublimation temperature. This method is specically adapted for drugs with
low sublimation temperatures and thermal stability. This method is quite
successful; the lling rate can reach 100% (Hirahara et al., 2000) provided
the SWCNT surfaces are adequately clean.
3. In situ lling: SWCNTs are synthesized while the lling material or drug is
sublimed, typically during the electric arc process. For example, using
various carbon anodes doped with C

60

to form peapods is being tried

(Monthioux et al., 2001). However, yields were found to be very low by this
route, probably because of the high speed of the transient phenomena and
the restricted volume while SWCNT formation occurs in the plasma. This
provides little chance for the potential ller to actually enter the SWCNT
cavity before the closing of the tubule while it grows, specically considering
that a closed tip growth model generally accepted mechanism for the SWCNT
formation.
4. Filling via liquid phase: SWCNTs, along with the ller in molten state, are
put together in a sealed ampoule. In this case, the capillary eect occurs
despite the nanometric diameter of the SWCNTs. It is necessary to have a
molten compound with a suciently low surface tension and low melting
temperature to avoid undesirable eects, such as early closing of the
previously opened carbon structure caused by an excessive melting
temperature (Govindaraj et al., 2001). One way is to ll the tubes with molten
salts and to reduce the salt using hydrogen gas, although it remains to be

ascertained whether the reduction rate is 100%. Samarium oxide has been
lled into MWCNTs by this method.
5. Solution phase chemistry has the advantage that without heat treatment,
the drug can be lled at room temperature. SWCNT material is soaked in a
solution of the compound to be inserted using a suitable solvent, depending
on the llers chemical composition and the specic requirement of the
process. As mentioned previously, the elemental state is obtained by
reducing the ller by hydrogen gas. Using this method, Sloan et al. (1998)
have lled SWCNTs with ruthenium.
6. Nanoextraction and nanocondensation: Most drugs neither evaporate nor
sublime, but rather degrade at elevated temperatures. Therefore, a new
method of incorporating drugs into SWCNTs at room temperature is
nanoextraction or nanocondensation.
For nanoextraction: SWCNTs are heat treated at 1780C in a vacuum for 5
hours and then further heated in an oxygen atmosphere at 570C for about
10 minutes. This heat treatment enlarges the diameter of the SWCNTs from
1 nm or less to 1 nm or more [in a study by Yudasak et al. (2003), about
50% of them had diameters >2 nm].
For nanoextraction, guest molecules must have a poor anity to the
solvent, but a strong anity to the CNTs. Also, the solvent, must have a
poor anity to CNTs. To demonstrate nanoextraction, C

60

crystallites (1

mg) were added to ethanol (10 mL) and ultrasonicated for 3 minutes and
then SWCNTs (1 mg) were added. This mixture of SWCNTs, C

60 ,

and

ethanol was kept for 1 day at room temperature. The solubility of C

ethanol is about 0.001 mg/mL (Kimata et al., 1993); hence, C

60

60

in

crystallites

could hardly dissolve and remained at the bottom of the ethanol solution
or suspended in it. After 1 day, the SWCNTs were taken out of the mixture
and air dried at room temperature. Transmission electron microscopy
(TEM) showed that C

60

molecules were incorporated inside the SWCNTs (C

60 ) n.

Nanocondensation: To prepare (C

60 )

SWCNTs through nanocondensation,

10 mL of C60-toluene standard solution (2 to 8 mg/mL) is dropped onto

SWCNTs placed on a grid disk (a TEM sample holder) kept on a lter paper
to soak the excess solution as quickly as possible (Ruo et al., 1993). The
grid disks are usually about 3 mm in diameter and about 0.035 mm thick
and are made up of copper with carbon.

Peapods can be applied to drug-delivery systems by replacing C

60

with

molecules having medicinal eects.

7. Opening of MWCNTs in a SCW medium creates an alternative possibility
for lling. However, for lling of MWCNTs, the very important criterion is the
surface tension threshold value of 100 to 200 mN/m. Also, there must be a
route for escape of gas or air trapped in the MWCNTs. Thus, if the MWCNTs
are opened inside a liquid with a low surface tension, the liquid should be
pulled unhindered by capillarity (Ebbesen, 1996; Ugarte et al., 1998). If
opening were achieved in SCW, it would be a useful mode to ll the desired
compounds soluble in SCW.
Because most of the modied compounds are soluble in super critical uid, it
will be an ecient medium for drug delivery by lling the nanotubes with
desired drugs.
So far, CNTs have been lled with halides, oxides, C

60 ,

heavy metals, gases

such as hydrogen, carbohydrates, DNA, enzymes, and other proteins. But

none of the drugs has yet been loaded or lled in CNTs.
24.7.1.5. DRUG RELEASE
Drug releases from nanoparticles to the site of action and subsequent
biodegradation are important for developing a successful formulation.
Moreover, the drug should be released from the nanoparticles at the desired
rate and cycle (Kumaresh et al., 2001; Mathiowitz et al., 1997). The release
rates of nanoparticles depend on:
Desorption of the surface-bound or adsorbed drug
Diusion through the nanoparticle matrix
Diusion (in case of nanocapsules) through the polymer wall
Nanoparticle matrix erosion
A combined erosion and diusion process (Hu et al., 2003; Kreuter, 1994a &
b).
Thus, diusion and biodegradation govern the process of drug release. After
the release of the drug, it is important that:

The particles inserted into the living system should preserve and protect
the drug from any degradation until they reach the site of action.
The drug should not get released until it reaches the sites of action .
The drug should be released at a rate that achieves the desired
therapeutic eect on a continuous basis.
It is of utmost importance to decide the type of drug release cycle to be
applied (e.g., constant, cyclic), depending on the environmental conditions.
The particles should recognize the site of action; this mostly depends on
the choice of antibodies attached to the nanoparticle along with the drug.
If desired, the nanoparticles should have the ability to get bound or
associated with the sites of action.
An in vitro drug release studies may give a detailed insight into the problems
and parameters associated with the release of drugs. However, in many
cases, the in vitro release cannot be correlated with the in vivo situation
(Park, 2002). In vitro drug release may be studied with a variety of methods
(Hu et al., 2003b).
Because of the small size of the nanoparticles, the separation of the
releasing particles from the rest of the sample represents a major problem.
In principle, this separation can be achieved either by ultracentrifugation or
by membrane separation using articial or biologic membranes, dialysis
bags, ultraltration, and centrifugal ultraltration.
All of these techniques have a common disadvantage that a signicant time
lapse exists between the immediate release from the particle and the time of
sampling because ultraltration, membrane diusion, ultracentrifugation,
and so on, are time-consuming processes. During this time lapse, the release
continues; therefore, it is not possible to obtain real-time release rates.
A very good alternative to study the release is the use of substances that
change their analytical prolefor instance, colorby moving from a
hydrophobic to a hydrophilic environment when traversing from the
nanoparticle into the release medium.
24.7.1.6. BIODEGRADATION

OF

DRUGS

Finally, when the drug is released, the nanoparticles should get degraded or
removed from the body. Biodegradation of nanoparticles is a very important
requirement for most therapeutic uses. Biodegradation has a profound
inuence on the drug release rate. In addition, with the possible exception of
vaccines, the nanoparticle or the carrier material has to be eliminated rather
rapidly to avoid accumulation in the body. However, degradation of
nanocarbon in living systems still remains an illusive system that has not yet
been worked out.

24.8. Progress Made So Far in Using Carbon Nanomaterial for

Drug Delivery
One of the important questions that scientists working with CNM to be used
as a drug-delivery vehicle is whether it can safely traverse through cells.
Bianco et al. (2005) showed that CNTs are adept at entering the nuclei of
cells; hence, they can be used as nanodelivery vehicle. They modied the
CNTs by heating them for several days in di-methyl formamide, which enabled
short linking chains of tri-ethylene glycol (TEG) to be attached. Then a small
peptide was bonded to the TEG molecule. When the modied CNTs were
mixed with cultures of human broblast cells, they rapidly entered and
migrated toward the nucleus. At low doses, the CNTs appeared to leave the
cells unharmed, but as the concentration was increased, cells began to die.
Although the use of CNM is in its infancy in the delivery of drugs,
researchers have started to believe that one day they may be able to use
CNTs to deliver drugs and vaccines. A wide range of dierent molecules
could be attached to the CNTs, increasing the possibility of an easily
customized way of ferrying molecules into the cells.
The basic concept for using CNTs in vaccine delivery is to link the antigen to
the CNTs while retaining their conformation and thereby inducing an
antibody response with the correct specicity. In addition, CNTs should not
trigger a response by the immune system (i.e., they should not possess
intrinsic immunogenicity) (Pantarotto et al., 2003a).
One can imagine that in the distant future, instead of receiving a vaccine
shot with a syringe, a patient may lick a lollipop coated with functionalized
CNTs acting as a vaccine-delivery system. CNTs have already been used to
build a computer, so the day is not far o when they can be applied to

improved drug-delivery systems or can travel to the brain after being

inhaled.

24.9. Possible Drawbacks in the Use of Carbon Nanomaterial for

Drug Delivery
The use of carbon in therapeutic systems has begun with many
apprehensions. Its suitability has been a big question mark in the mind of
many scientists. One of the apprehensions is that use of nanosized material
in medicine poses unique problems; they can be cleared out of the body
before they complete their mission. Moreover, they also have a large surface
area relative to their volume, which may allow unwanted friction.
As far as the breakdown products of nanocarbon are concerned, our
knowledge at the moment is almost negligible, and it needs further research.
The brighter side is that looking at the possibilities and applicability of CNMs
in drug delivery, scientists have gotten actively involved in solving these
issues.

24.10. Summary
In this chapter, the possibility of using CNMs as tools or vehicles to deliver
drugs in desired amounts to sites of action have been discussed. Various
properties that make CNMs a possible drug carrier have also been explored.
Finally, dierent processes involvedfrom tailoring CNMs to the desired size,
loading and releasing the drug, and the biodegradation of CNMshave been
discussed.
Citation
EXPORT

Maheshwar Sharon; Madhuri Sharon: Carbon Nano Forms and Applications. Carbon
Nanomaterial As a Nanosyringe: A Near-Future Reality, Chapter (McGraw-Hill
Professional, 2010), AccessEngineering

2012 The McGraw-Hill Companies. All rights reserved.

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