**5. Selected examples for preparation of carbon nanotube based therapeutics**

In the above CNTs for drug delivery section, we described the functionalization of CNTs with drugs or targeting molecules. These preparations are usually applied directly via intra‐ venous delivery route, which is the most widely used route of drug administration. Alterna‐ tive to the intravenous drug administration, some other routes of drug administrations are also important for certain specific applications. Different formulations of CNT-based thera‐ peutics have also been developed to suit the specific routes of administration. Here, we re‐ port several novel cases of CNTs applications for oral and transdermal delivery routes.

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

mal drug delivery. It has been shown that this CNT-membrane was very effective for treatment of drug abuse and addiction [109]. To prepare the CNT-membrane, MWNTs were firstly functionalized with negatively charged molecule containing sulphonate (−SO3-) to have a high charge density on the surface of CNTs, which is necessary to get efficient elec‐ tro-osmosis pumping effect. By this functionalization strategy, CNT-membrane achieves dramatically fast flow through CNT cores, high charge density, and highly efficient electro‐ phoretic pumping effect. These membranes were the integrated with a nicotine formulation to obtain switchable transdermal nicotine delivery rates on human skin (in vitro). The trans‐ dermal nicotine formulated CNT-membrane was able to successfully switch between high level and low level fluxes that coincide with therapeutic demand levels for nicotine cessa‐

Carbon Nanotubes for Use in Medicine: Potentials and Limitations

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tion treatment. These programmable devices cause minimal skin irritation [109].

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

CNTs have recently gained much interest in the field of medicine.

for future clinical applications of CNT-based therapeutics.

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,

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 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 be used for other delivery routes as well.

**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‐ capsule [108].

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

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‐ mal drug delivery. It has been shown that this CNT-membrane was very effective for treatment of drug abuse and addiction [109]. To prepare the CNT-membrane, MWNTs were firstly functionalized with negatively charged molecule containing sulphonate (−SO3-) to have a high charge density on the surface of CNTs, which is necessary to get efficient elec‐ tro-osmosis pumping effect. By this functionalization strategy, CNT-membrane achieves dramatically fast flow through CNT cores, high charge density, and highly efficient electro‐ phoretic pumping effect. These membranes were the integrated with a nicotine formulation to obtain switchable transdermal nicotine delivery rates on human skin (in vitro). The trans‐ dermal nicotine formulated CNT-membrane was able to successfully switch between high level and low level fluxes that coincide with therapeutic demand levels for nicotine cessa‐ tion treatment. These programmable devices cause minimal skin irritation [109].
