**6. Potentials and limitations of carbon nanotubes in medicine**

**5.1. Carbon nanotube based therapeutics delivery using artificial cells: oral delivery**

be used for other delivery routes as well.

300 Syntheses and Applications of Carbon Nanotubes and Their Composites

capsule [108].

For many therapeutics, oral and targeted delivery are challenge. One way to deliver them at the targeted site is by novel methods of encapsulating them in polymeric artificial cells. Artificial cells are vesicles made by polymeric membranes. They can mimic certain func‐ tions of biological cells. The size of artificial cells ranged from nanometer to hundreds of micrometer [105]. The membranes of artificial cells are usually semi-permeable that allows for exchange of small molecules and prevention of passage of large substances across it. Up to date, artificial cells have been applied for encapsulation biologically active agents, includ‐ ing enzymes, hormones, drugs, even live bacteria cells for in-vivo delivery. Currently a couple of artificial cells have been applied clinically [106]. The advantages of artificial cells include protection of the cargos from immune elimination in the body, targeted delivery of cargos to desired sites and increasing cargo solubility [106]. In a first feasibility study, func‐ tionalized CNTs have been encapsulated in artificial cell made from biocompatible polymer‐ ic membrane for target specific delivery. The polymeric membrane was assembled with three layers of polymers, alginate-poly-L-lysine-alginate (APA), via electrostatic association (fig‐ ure 6). Artificial cells protected CNT therapeutics from degradation by the harsh environ‐ ments [107]. PH degradation profile of the polymeric membrane of artificial cells can be adjusted by composition of polymers, which allows the breakdown of the artificial cells and release of CNT therapeutics to desired sites. This system is ideal for oral delivery, and can

**Figure 6.** Alginate-poly-L-lysine-alginate (APA) microcapsules encapsulatingcarbon nanotubes. The calcium ions are responsible for cross-linking of the alginate monomeric units trapping the carbon nanotubes into the core of micro‐

One of the most important areas of transdermal drug delivery (TDD) is in addiction treat‐ ment. Nicotine TDD has been widely used for smoking cessation programs. However, these traditional transdermal patches could not provide variable drug delivery rates. Some TDD has the capability to provide variable and programmable delivery rates, however, it needs a strong electric current across the human skin, which can cause serious skin irritation. Re‐ cently, the membranes prepared by functionalized CNTs have been employed in transder‐

**5.2. Carbon nanotube based membrane: transdermal drug delivery**

CNTs are being highly explored in the fields of targeted drug delivery, nanoscaffold for tis‐ sue engineering, biomedical imagining and detecting for disease treatment and health moni‐ toring. The use of CNTs in drug delivery, detection and tissue engineering has shown the potentials to revolutionize medicine. CNTs affords for a large amounts of payloads for spe‐ cific-targeting and drug delivery. With their intrinsic properties, the CNTs have potential for building-up multifunctional nanodevices for simultaneous therapeutic delivery and detec‐ tion. Current cancer therapies (eg. radiation therapy, and chemotherapy) are usually painful and less efficient since they kill normal cells in addition to cancer cells, and therefore, pro‐ ducing adverse side effects and resistance. The CNT-based drug delivery systems have shown efficient tumor-targeting, and they can effectively kill cancer cells with a dosage low‐ er than conventional drugs used, however significantly reduces side effects. Current CNTbased nanoscaffolds are very advantages for stem cells therapy in that they can modulate the stem cell growth and differentiation in a more controlled and desirable manner. Thus, CNTs have recently gained much interest in the field of medicine.

Although very useful, CNTs exist some limitations. Firstly, pristine CNTs, being metallic in their nature, are insoluble and they form large bundles or ropes in many solvents, including water and most solvents, so they cannot be used directly in biomedical applications. Much work has been done to prepare them for use in medicine. Secondly, the CNTs are not homo‐ genous in their sizes (both diameters and lengths), which could be a problem for generation of reproducible results that allows evaluation of the biological activity relating to specific structures. Up to date, tremendous efforts have been put in surface functionalization of CNTs for use in medicine. This includes numerous effective methods for covalent or noncovalent modification of CNTs as to disperse them into aqueous solutions and to attach functional molecules for therapeutic applications. However, in terms of homegenecity of CNTs. Not much work has been done so far. We propose that attentions are needed to de‐ velop the methods for generation of CNTs with homogeneous size, which is very important for future clinical applications of CNT-based therapeutics.

As a novel nanomaterial of great potentials in medicine, the toxicology of CNTs has received much attention in recent years. Pristine CNTs are very light powders and they can enter the body through inhalation via the respiratory tract, ingestion via the gastrointestinal tract or, dermal absorption via the skin. Following entering, CNTs distribute rapidly in the central and peripheral nervous system, lymphatic and blood circulation and potentially cause toxic effects in a variety of tissues and organs that they reach, such as heart, spleen, kidney, bone marrow and liver, etc. Toxicity of CNTs has been evaluated in a variety of cell or animal models for assessing pulmonary, dermal and immune effects. However, the published re‐ sults have not led to any consensus on the toxicity profile of pristine or functionalized SWNTs and MWNTs. Some investigators reported that pristine SWNTs that were purified by acid treatment demonstrated no acute toxicity, as opposed to non-purified CNTs, howev‐ er, they induced reactive oxygen species (ROS) in human lung carcinoma epithelial A549 cells and NR8383 cells [110]. Others demonstrated that pristine SWNTs, either acid-treated or non-treated, were capable of increasing chromosome and DNA damage, and oxidative stress in macrophage cell lines [111, 112].

and length of tubes, metal impurities and functionalization methods etc. Moreover, different analysis methods used in the evaluation CNTs toxicity studies also cause disparities. De‐ spite these disparities, there is a broad agreement that well-dispersed CNTs have little or no toxicity both in-vitro and in-vivo, and therefore are useful for biomedical applications. Final‐ ly, an urgent need has been proposed for long-term studies on the absorption, deposition, metabolism and excretion (ADME) of CNTs. Only after the uncertainty on CNT toxicity is

This work is partially supported by research grant to Satya Prakash from Canadian Insti‐ tutes of Health Research (CIHR) (MOP 93641). W. Shao and L. Rodes acknowledges Doctor Training Award from Fonds de Research Sante (FRSQ). A. Paul acknowledges Post-Doctoral

, Laetitia Rodes1

1 Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial cells and Organs Research Centre, Faculty of Medicine, McGill

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[4] Ando, Y. (2010). Carbon nanotube: the inside story. *J Nanosci Nanotechnol*, 10(6),

networks. *Journal of the American Chemical Society*, 5990-5995.

and Satya Prakash1\*

Carbon Nanotubes for Use in Medicine: Potentials and Limitations

http://dx.doi.org/10.5772/51785

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resolved, the CNT-based therapeutics can be possible applied clinically.

, Mai Yiyong2

\*Address all correspondence to: satya.prakash@mcgill.ca

2 Department of Chemistry, McGill University, Canada

sensing. *Nanoscale*, 3(5), 1949-1956.

**Acknowledgements**

Award from FRSQ.

**Author details**

University, Canada

**References**

3726-3738.

, Paul Arghya1

Wei Shao1

In contrast to raw or acid treated CNTs, the well-dispersed CNTs with high levels of surface functionalization can reduce the toxicity of MWNTs. One study demonstrated that taurine-MCWNTs in low and medium doses induced slight and recoverable pulmonary inflamma‐ tion in mice, and are less toxic than raw MCWNTs [113]. This is supported by other studies indicating that the damage caused by non-PEGylated MWNTs is slightly more severe than that of PEGylated MWNTs [114]. Furthermore, administrations of high doses of PL-PEG functionalized SWNTs following intravenous injection did not lead to acute or chronic toxic‐ ity in nude mice, albeit SWNTs persisted within liver and spleen macrophages for 4 months in mice without apparent toxicity [115] and the SWNTs-PL-PEG were excreted from mice via the biliary and renal pathways [116]. It is hypothesized that the van der Waals forces on the surfaces of pristine CNTs cause hydrophobic interactions between CNTs, resulting in ag‐ gregation and network formation, which further induce prolonged toxicity. Thus, function‐ alization of CNTs overcomes the aggregate-forming surface properties of CNTs, and therefore, reduces toxicity.
