Carbon Nanomaterial as a Nanosyringe

8/16/2019 Carbon Nanomaterial as a Nanosyringe

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24. Carbon Nanomaterial As a Nanosyringe: A Near-

Future Reality

24.1. Introduction

The application of nanotechnology has tremendous potential in health care,

particularly for the development of better pharmaceuticals. Nanotechnology-

enabled drug delivery has already been successful in delivering drugs to

specific 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 efficacy of a drug can be increased if it is

delivered to its target selectively and if its release profile 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 exemplified by

breakthroughs in bio-directed nanosynthesis, nanoassembly, and nano-aided

biologic recognition. Efforts are currently focused on searching f or 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 cancer’s location in the

body, and delivering anticancer drugs specifically 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

Carbon Nanomaterial As a Nanosyringe: A Near-

Future Reality

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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 efficacy 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 effects of the drugs. Dendrimers, silica-

coated 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 efficient way possible. Nanoparticles, chiefly

because of their small particle size, offer 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 μm (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 effect 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


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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. Definition of Nanoparticles for Pharmaceutical and

Medical Purposes

Nanoparticles for pharmaceutical purposes are defined by Kreuter (1994b) in

the Encyclopedia of Pharmaceutics Technology as “solid colloidal particles

ranging in size from 1–1000 nm (1 μm). 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 different 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

Ehrlich’s idea and developed the first nanoparticle for drug-deliverypurposes (Birrenbch and Speiser 1976; Kopf et al., 1976, 1977). These

nanoparticles were produced by emulsion polymerization of acrylamide cross-

linked with N,N’-methylene bis acrylamide in hexane.

Zolle et al. (1970) used another process, denaturation of albumin dissolved in

water and emulsified in hot cottonseed oil, to produce nanoparticles. 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 first successful drug targeting with

nanoparticles by incorporation of magnetite particles into similar albumin

nanoparticles and the use of a magnetic field. They substituted a more

efficient 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

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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 brain’s 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, fibrous, and bead-like structures

named CNTs, carbon nanofibers (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. C ARBON N ANOTUBES

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.


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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 neverpreviously 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 μm. The arrangement of carbon in an SWCNT can beof 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 μm. The individual graphene sheets are

separated by about 0.34 nm.

24.4.1.2. C ARBON N ANOFIBERS

CNFs are filaments without a lumen. They can be produced in various

shapes, including straight, coiled, cactus, cauliflower, octopus, stacked, or

fish-bone (herring-bone) shaped.

24.4.1.3. C ARBON N ANOBEADS

CNBs are spherical, hollow structures. When five 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 Purification of Carbon Nanomaterial

The synthesis, opening, and thinning of SWCNTs, MWCNTs, and

nanomaterials are topics of immense interest owing to their potential


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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 purification

of synthesized CNMs are given in Chapters 2 to 5.

Synthesis of CNM involves use of catalysts, which often remain along with the

finally 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 purification, care is taken to remove the

amorphous carbon.

Various purification procedures have been reported in the literature

(Monthioux et al., 2001). Most of them are done by using acids such as HCl or

H SO or other oxidizing reactants such as H O . These purification

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 350°C to defunctionalize them in the

process, leaving purified 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

affect drug delivery include their chemical reactivity, electrical conductivity,

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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 modification of

either the sidewall or end caps is possible.

Although CNMs are usually insoluble material, the solubility of CNTs in

different 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 influenced 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 flexible; 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 confinement effect and large surface-to- volume 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.


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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

filled 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. OPENING THE CLOSED ENDS OF C ARBON N ANOTUBES

CNT opening has been demonstrated to be a side effect of the various acid-based purification 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

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reasons for initiation of oxidation at the tips or caps (Hwang, 1995), thus

opening the closed ends.

24.7.1.2. CUTTING OR T AILORING C ARBON N ANOMATERIAL TO THE DESIRED SIZE

Shorter tubes have found many applications, such as in field 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 fine

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). Different-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 , 374°C; P , 3200 psi), where T 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 efficient nonpolar solvent.

Nonpolar organics are completely soluble in SCW in the presence of oxygen

and could be rapidly and efficiently oxidized to carbon dioxide and water in a

single homogeneous fluid 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.

c c c

c

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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 24-1. Scanning electron micrograph of carbon nanofibers

before (A) and ball milling after (B).

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.)

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>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 fillers or to enhance the solubility of CNTs in varioussolvents.

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 flouronanotubes 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 different 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., ~750°C

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 (Hoffmann 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


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incorporated into a hydrophobic nanoparticle without difficulties 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 filling

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 specifically adapted for drugs with

low sublimation temperatures and thermal stability. This method is quite

successful; the filling rate can reach 100% (Hirahara et al., 2000) provided

the SWCNT surfaces are adequately clean.

3. In situ filling: SWCNTs are synthesized while the filling material or drug is

sublimed, typically during the electric arc process. For example, using

various carbon anodes doped with C 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 filler to actually enter the SWCNT

cavity before the closing of the tubule while it grows, specifically considering

that a closed tip growth model generally accepted mechanism for the SWCNT

formation.

4. Filling via liquid phase: SWCNTs, along with the filler in molten state, are

put together in a sealed ampoule. In this case, the capillary effect occurs

despite the nanometric diameter of the SWCNTs. It is necessary to have a

molten compound with a sufficiently low surface tension and low melting

temperature to avoid undesirable effects, such as early closing of the

previously opened carbon structure caused by an excessive melting

temperature (Govindaraj et al., 2001). One way is to fill the tubes with molten

salts and to reduce the salt using hydrogen gas, although it remains to be

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ascertained whether the reduction rate is 100%. Samarium oxide has been

filled into MWCNTs by this method.

5. Solution phase chemistry has the advantage that without heat treatment,

the drug can be filled at room temperature. SWCNT material is soaked in a

solution of the compound to be inserted using a suitable solvent, depending

on the filler’s chemical composition and the specific requirement of the

process. As mentioned previously, the elemental state is obtained by

reducing the filler by hydrogen gas. Using this method, Sloan et al. (1998)

have filled 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 1780°C in a vacuum for 5

hours and then further heated in an oxygen atmosphere at 570°C 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 affinity to the

solvent, but a strong affinity to the CNTs. Also, the solvent, must have a

poor affinity to CNTs. To demonstrate nanoextraction, C 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 , and

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

ethanol is about 0.001 mg/mL (Kimata et al., 1993); hence, C 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 molecules were incorporated inside the SWCNTs (C

) .

Nanocondensation: To prepare (C ) SWCNTs through nanocondensation,

10 μ 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 filter paperto soak the excess solution as quickly as possible (Ruoff 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.

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

molecules having medicinal effects.

7. Opening of MWCNTs in a SCW medium creates an alternative possibility

for filling. However, for filling of MWCNTs, the very important criterion is the

surface tension threshold value of 100 to 200 mN/m. Also, there must be aroute 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 fill the desired

compounds soluble in SCW.

Because most of the modified compounds are soluble in super critical fluid, it

will be an efficient medium for drug delivery by filling the nanotubes with

desired drugs.

So far, CNTs have been filled with halides, oxides, C , heavy metals, gases

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

none of the drugs has yet been loaded or filled in CNTs.

24.7.1.5. DRUG R ELEASE

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

Diffusion through the nanoparticle matrix

Diffusion (in case of nanocapsules) through the polymer wall

Nanoparticle matrix erosion

A combined erosion and diffusion process (Hu et al., 2003; Kreuter, 1994a &

b).

Thus, diffusion and biodegradation govern the process of drug release. After

the release of the drug, it is important that:

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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 effect 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 orassociated 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 artificial or biologic membranes, dialysis

bags, ultrafiltration, and centrifugal ultrafiltration.

All of these techniques have a common disadvantage that a significant time

lapse exists between the immediate release from the particle and the time of

sampling because ultrafiltration, membrane diffusion, 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 profile—for instance, color—by moving from a

hydrophobic to a hydrophilic environment when traversing from thenanoparticle into the release medium.

24.7.1.6. BIODEGRADATION OF DRUGS


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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

influence 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 modified 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 modified CNTs were

mixed with cultures of human fibroblast cells, they rapidly entered andmigrated 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 different 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 specificity. 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 vaccineshot 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 off when they can be applied to


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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, different processes involved—from tailoring CNMs to the desired size,

loading and releasing the drug, and the biodegradation of CNMs—have been

discussed.

Citation

Maheshwar Sharon; Madhuri Sharon: Carbon Nano Forms and Applications. Carbon

Nanomaterial As a Nanosyringe: A Near-Future Reality, Chapter (McGraw-Hill

Professional, 2010), AccessEngineering

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