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Carbon Nanotubes as Nanocarriers for Controlled Drug Delivery
| Content Provider | Scilit |
|---|---|
| Copyright Year | 2016 |
| Description | Book Name: Controlled Release Systems |
| Abstract | Figure 12.1 (A) Schematic representation of a SWCNT. (B) Transmission electron microscopy (TEM) and (C) high-resolution transmission electron microscopy (HRTEM) images of MWCNTs. Drug delivery systems have been investigated to increase the efficacy of therapeutic molecules without adversely affecting the surrounding tissues, resulting in the minimization of undesirable side effects. Current efforts focus on cancer therapy to overcome poor distribution and penetration of anticancer drugs into tumor tissues, nonspecificity, and rapid elimination. In addition, the limitedsolubility and stability of some drugs render their administration a challenge. The drug release kinetics is determinant for maintaining high drug concentration at the desired site but not in the bloodstream to avoid systemic toxicity. Therefore, the major challenges lie on high drug-loading capacity, high drug retention during the delivery process, and the ability to release the drug on command. In this context, CNTs present many advantages as a drug delivery system, in particular due to their high surface area and empty cavity available for loading of drugs. Their structural properties, tubular shape, and mechanical strength associated with flexibility allow them to easily cross biological barriers and to be internalized in cells with minimal cytotoxicity (Kostarelos et al., 2007). When CNTs are functionalized with suitable molecules to make them dispersible in physiological solutions, to disaggregate and shorten them, their possible toxicity is alleviated (Dumortier et al., 2006; Ali-Boucetta et al., 2013). Moreover, their electronic and optical properties bring additional functionalities to CNTs as carriers in comparison to other drug delivery systems. These properties can be exploited for diagnostic, imaging, and therapeutical purposes, including photothermal therapy (Iancu and Mocan, 2011). Functionalized CNTs can be eliminated via renal and/or fecal excretion, depending on the type of functionalization (Singh et al., 2006; Liu et al., 2008b). Therapeutic molecules can be conjugated to CNTs on their sidewall via covalent bonding (Singh et al., 2009) or noncovalent interactions (Karousis et al., 2010). As covalent grafting of drugs onto CNTs may change their pharmacological activity, strategies have been developed where cleavable bonds are inserted to allow their release from the nanotube sidewall triggered by enzymes (Chaudhuri et al., 2010; Kam et al., 2005a; Liu et al., 2008a; Samorí et al., 2010). Supramolecular interactions between adsorbed molecules and the nanotube surface can be modulated by pH or external stimuli such as NIR irradiation and heating, leading to drug release. Alternatively, the inner hollow cavity of CNTs offers space for encapsulation of molecules (so-called endohedral functionalization), provided that their ends are open to make the empty core accessible (Khlobystov et al., 2005). In this case, the loaded drugs are protected from deactivation before reaching the target sites. External boosts, including NIR irradiation or amagnetic field, can induce unloading of entrapped molecules. A few approaches have been designed to seal the ends of CNTs with fullerenes or gold nanoparticles (NPs) and control the removal of the caps. In this chapter, we aim to give an initial overview on endohedral functionalization of CNTs for controlled release of drugs. Different strategies have been explored to trigger the release of therapeutic molecules loaded inside CNTs. Another part is dedicated to the release of drugs adsorbed on the nanotube surface by different stimuli such as pH, NIR light, and heat. Finally, the last part focuses on the sidewall functionalization of CNTs with drugs via enzyme-cleavable linkers. 12.2 Endohedral Functionalization of CarbonNanotubes for Controlled Release of DrugsEncapsulation of molecules inside the empty cavity of CNTs presents many advantages such as protection from deactivating agents or conditions that could impact their stability. In addition, there is no need of covalent bonding as it can be the case for sidewall functionalization; therefore the structural integrity of the drug compounds is not affected. It has been demonstrated theoretically and experimentally that the inner core of CNTs has a higher binding energy for adsorption of molecules compared to the external sidewall (Kondratyuk and Yates, 2007; Simonyan et al., 2001). Although a series of organic molecules (Koshino et al., 2007; Liu et al., 2007b; Takenobu et al., 2003; Yanagi et al., 2006), inorganic crystals (Hong et al., 2010; Meyer et al., 2000), and NPs (Castillejos et al., 2009) has been inserted inside the nanotube cavity, investigations on the encapsulation of drugs are still in an early stage. MWCNTs seem to be more appropriate for filling with bioactive compounds as they possess a larger internal diameter in comparison with SWCNTs, although loading of molecules inside SWCNTs has already been performed (Kang et al., 2009c; Monthioux, 2002; Morgan et al., 2002; Tripisciano et al., 2009; Yao et al., 2011). Furthermore, the external surface of MWCNTs can be functionalized without inducing defects that could lead to the leakage of the embedded molecules as it could be the case for SWCNTs. Nevertheless, the loading and release are rather difficult to control. It is crucial that the cargo molecules are released atthe desired location. The molecules have to possess low surface tension to facilitate their loading inside CNTs by capillary or van der Waals forces. Due to high-energy barrier at the open ends of nanotubes, the encapsulation process is often irreversible (Hilder and Hill, 2009). However, slow diffusion of incorporated drugs has been observed in some cases and exploited for sustained release in cells. In a few studies, smart strategies have been developed to block the nanotube ends and/or trigger the drug release. 12.2.1 Sustained Release of Encapsulated DrugsThe anticancer drug... |
| Related Links | https://api.taylorfrancis.com/content/chapters/edit/download?identifierName=doi&identifierValue=10.1201/b19860-14&type=chapterpdf |
| Ending Page | 274 |
| Page Count | 30 |
| Starting Page | 245 |
| DOI | 10.1201/b19860-14 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2016-01-05 |
| Access Restriction | Open |
| Subject Keyword | Book Name: Controlled Release Systems Carbon Nanotubes Type of Functionalization Efficacy Mwcnts Cnts Present Empty Cavity Covalent Bonding Open Ends |
| Content Type | Text |
| Resource Type | Chapter |
