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CARBON NANOTUBES: AN APPROACH TO NOVEL DRUG DELIVERY SYSTEM
M. H. Alai et al.
International Journal of Pharmaceutical Sciences and Research , 2012,
Abstract: Carbon nanotubes are cylindrical carbon molecules have novel properties, making them potentially useful in many applications in nanotechnology, electronics, optics, and other fields of material science as well as potential uses in architectural fields. They have unique electronic, mechanical, optical and chemical properties that make them good candidates for a wide variety of applications, including drug transporters, new therapeutics, delivery systems and diagnostics. Their unique surface area, stiffness, strength and resilience have led to much excitement in the field of pharmacy. Nanotubes are categorized as single-walled nanotubes, multiple walled nanotubes. Various techniques have been developed to produce nanotubes in sizeable quantities, including arc discharge, laser ablation, chemical vapor deposition. They can pass through membranes, carrying therapeutic drugs, vaccines and nucleic acids deep into the cell to targets previously unreachable. Purification of the tubes can be divided into a couple of main techniques: oxidation, acid treatment, annealing, sonication, filtering and functionalization techniques. The main problem of insolubility in aqueous media has been solved by developing a synthetic protocol that allows highly water-soluble carbon NTs to be obtained. The modifications are done to improve efficiency of carbon nanotubes by formulating luminescent carbon nanotubes, ultrathin carbon nanoneedles, magnetically guided nanotubes. The application of carbon nanotube in tissue engineering, drug carrier release system, wound healing, in cancer treatment and as biosensor. Researchers have recently developed a new approach to Boron Neutron Capture Therapy in the treatment of cancer using substituted Carborane-Appended Water-Soluble single-wall carbon nanotubes.
Drug delivery with carbon nanotubes for in vivo cancer treatment  [PDF]
Zhuang Liu,Kai Chen,Corrine Davis,Sarah Sherlock,Qizhen Cao,Xiaoyuan Chen,Hongjie Dai
Physics , 2008, DOI: 10.1158/0008-5472
Abstract: Chemically functionalized single-walled carbon nanotubes (SWNTs) have shown promise in tumor targeted accumulation in mice and exhibit biocompatibility, excretion and little toxicity. Here, we demonstrate in-vivo SWNT drug delivery for tumor suppression in mice. We conjugate paclitaxel (PTX), a widely used cancer chemotherapy drug to branched polyethylene-glycol (PEG) chains on SWNTs via a cleavable ester bond to obtain a water soluble SWNT-paclitaxel conjugate (SWNT-PTX). SWNT-PTX affords higher efficacy in suppressing tumor growth than clinical Taxol in a murine 4T1 breast-cancer model, owing to prolonged blood circulation and 10-fold higher tumor PTX uptake by SWNT delivery likely through enhanced permeability and retention (EPR). Drug molecules carried into the reticuloendothelial system are released from SWNTs and excreted via biliary pathway without causing obvious toxic effects to normal organs. Thus, nanotube drug delivery is promising for high treatment efficacy and minimum side effects for future cancer therapy with low drug doses.
A new era of cancer treatment: carbon nanotubes as drug delivery tools  [cached]
Madani SY,Naderi N,Dissanayake O,Tan A
International Journal of Nanomedicine , 2011,
Abstract: Seyed Yazdan Madani1, Naghmeh Naderi1, Oshani Dissanayake1, Aaron Tan1, Alexander M Seifalian1,21Centre for Nanotechnology and Regenerative Medicine, Division of Surgery and Interventional Sciences, University College London, UK; 2Royal Free Hampstead NHS Trust Hospital, London, UKAbstract: Cancer is a generic term that encompasses a group of diseases characterized by an uncontrolled proliferation of cells. There are over 200 different types of cancer, each of which gains its nomenclature according to the type of tissue the cell originates in. Many patients who succumb to cancer do not die as a result of the primary tumor, but because of the systemic effects of metastases on other regions away from the original site. One of the aims of cancer therapy is to prevent the metastatic process as early as possible. There are currently many therapies in clinical use, and recent advances in biotechnology lend credence to the potential of nanotechnology in the fight against cancer. Nanomaterials such as carbon nanotubes (CNTs), quantum dots, and dendrimers have unique properties that can be exploited for diagnostic purposes, thermal ablation, and drug delivery in cancer. CNTs are tubular materials with nanometer-sized diameters and axial symmetry, giving them unique properties that can be exploited in the diagnosis and treatment of cancer. In addition, CNTs have the potential to deliver drugs directly to targeted cells and tissues. Alongside the rapid advances in the development of nanotechnology-based materials, elucidating the toxicity of nanoparticles is also imperative. Hence, in this review, we seek to explore the biomedical applications of CNTs, with particular emphasis on their use as therapeutic platforms in oncology.Keywords: carbon nanotubes, cancer, photothermal therapy, drug delivery, cytotoxicity, near infrared
A new era of cancer treatment: carbon nanotubes as drug delivery tools
Madani SY, Naderi N, Dissanayake O, Tan A, Seifalian AM
International Journal of Nanomedicine , 2011, DOI: http://dx.doi.org/10.2147/IJN.S16923
Abstract: new era of cancer treatment: carbon nanotubes as drug delivery tools Review (9494) Total Article Views Authors: Madani SY, Naderi N, Dissanayake O, Tan A, Seifalian AM Published Date November 2011 Volume 2011:6 Pages 2963 - 2979 DOI: http://dx.doi.org/10.2147/IJN.S16923 Seyed Yazdan Madani1, Naghmeh Naderi1, Oshani Dissanayake1, Aaron Tan1, Alexander M Seifalian1,2 1Centre for Nanotechnology and Regenerative Medicine, Division of Surgery and Interventional Sciences, University College London, UK; 2Royal Free Hampstead NHS Trust Hospital, London, UK Abstract: Cancer is a generic term that encompasses a group of diseases characterized by an uncontrolled proliferation of cells. There are over 200 different types of cancer, each of which gains its nomenclature according to the type of tissue the cell originates in. Many patients who succumb to cancer do not die as a result of the primary tumor, but because of the systemic effects of metastases on other regions away from the original site. One of the aims of cancer therapy is to prevent the metastatic process as early as possible. There are currently many therapies in clinical use, and recent advances in biotechnology lend credence to the potential of nanotechnology in the fight against cancer. Nanomaterials such as carbon nanotubes (CNTs), quantum dots, and dendrimers have unique properties that can be exploited for diagnostic purposes, thermal ablation, and drug delivery in cancer. CNTs are tubular materials with nanometer-sized diameters and axial symmetry, giving them unique properties that can be exploited in the diagnosis and treatment of cancer. In addition, CNTs have the potential to deliver drugs directly to targeted cells and tissues. Alongside the rapid advances in the development of nanotechnology-based materials, elucidating the toxicity of nanoparticles is also imperative. Hence, in this review, we seek to explore the biomedical applications of CNTs, with particular emphasis on their use as therapeutic platforms in oncology.
Carbon Nanotubes in Biology and Medicine: in vitro and in vivo Detection, Imaging and Drug Delivery  [PDF]
Zhuang Liu,Scott Tabakman,Kevin Welsher,Hongjie Dai
Physics , 2009,
Abstract: Carbon nanotubes exhibit many unique intrinsic physical and chemical properties and have been intensively explored for biological and biomedical applications. In this review, we summarize the main results of our and other groups in this field and clarify that surface functionalization is critical to the behaviors of carbon nanotubes in biological systems. Ultra-sensitive detection of biological species with carbon nanotubes can be realized after surface passivation to inhibit the non-specific binding of bio-molecules on the hydrophobic nanotube surface. Electrical nanosensors based on nanotubes provide a label-free approach to biological detections. Surface enhanced Raman spectroscopy of CNT opens up a method of protein microarray with down to 1 fM detection sensitivity. In vitro and in vivo toxicity studies reveal that well water soluble and serum stable nanotubes are biocompatible, non-toxic and potentially useful for biomedical applications. In vivo biodistributions vary with the functionalization and possibly also sizes of nanotubes, with a tendency of accumulation in the reticuloendothelial systems, including the liver and spleen, after intravenous administration. If well functionalized, nanotubes may be excreted mainly through the biliary pathway in feces. Carbon nanotube-based drug delivery has shown promises in various in vitro and in vivo experiments including delivery pf small interfering RNA, paclitaxel and doxorubicin. Moreover, SWNTs with various interesting intrinsic optical properties have been used as novel photoluminance, Raman and photoacoustic contrast agents for imaging of cells and animals. Further multidisciplinary explorations in this field are promising and may bring new opportunities to the realm of biomedicine.
The application of carbon nanotubes in target drug delivery systems for cancer therapies  [cached]
Zhang Wuxu,Zhang Zhenzhong,Zhang Yingge
Nanoscale Research Letters , 2011,
Abstract: Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.
Biosafety of Non-Surface Modified Carbon Nanocapsules as a Potential Alternative to Carbon Nanotubes for Drug Delivery Purposes  [PDF]
Alan C. L. Tang, Gan-Lin Hwang, Shih-Jung Tsai, Min-Yao Chang, Zack C. W. Tang, Meng-Da Tsai, Chwan-Yao Luo, Allan S. Hoffman, Patrick C. H. Hsieh
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032893
Abstract: Background Carbon nanotubes (CNTs) have found wide success in circuitry, photovoltaics, and other applications. In contrast, several hurdles exist in using CNTs towards applications in drug delivery. Raw, non-modified CNTs are widely known for their toxicity. As such, many have attempted to reduce CNT toxicity for intravenous drug delivery purposes by post-process surface modification. Alternatively, a novel sphere-like carbon nanocapsule (CNC) developed by the arc-discharge method holds similar electric and thermal conductivities, as well as high strength. This study investigated the systemic toxicity and biocompatibility of different non-surface modified carbon nanomaterials in mice, including multi-walled carbon nanotubes (MWCNTs), single-walled carbon nanotubes (SWCNTs), carbon nanocapsules (CNCs), and C60 fullerene (C60). The retention of the nanomaterials and systemic effects after intravenous injections were studied. Methodology and Principal Findings MWCNTs, SWCNTs, CNCs, and C60 were injected intravenously into FVB mice and then sacrificed for tissue section examination. Inflammatory cytokine levels were evaluated with ELISA. Mice receiving injection of MWCNTs or SWCNTs at 50 μg/g b.w. died while C60 injected group survived at a 50% rate. Surprisingly, mortality rate of mice injected with CNCs was only at 10%. Tissue sections revealed that most carbon nanomaterials retained in the lung. Furthermore, serum and lung-tissue cytokine levels did not reveal any inflammatory response compared to those in mice receiving normal saline injection. Conclusion Carbon nanocapsules are more biocompatible than other carbon nanomaterials and are more suitable for intravenous drug delivery. These results indicate potential biomedical use of non-surface modified carbon allotrope. Additionally, functionalization of the carbon nanocapsules could further enhance dispersion and biocompatibility for intravenous injection.
Organic functionalization of single-walled carbon nanotubes (SWCNTs) with some chemotherapeutic agents as a potential method for drug delivery
Ardeshir Khazaei, Mohammad Navid Soltani Rad, Maryam Kiani Borazjani
International Journal of Nanomedicine , 2010, DOI: http://dx.doi.org/10.2147/IJN.S11146
Abstract: ganic functionalization of single-walled carbon nanotubes (SWCNTs) with some chemotherapeutic agents as a potential method for drug delivery Original Research (5765) Total Article Views Authors: Ardeshir Khazaei, Mohammad Navid Soltani Rad, Maryam Kiani Borazjani Published Date August 2010 Volume 2010:5 Pages 639 - 645 DOI: http://dx.doi.org/10.2147/IJN.S11146 Ardeshir Khazaei1, Mohammad Navid Soltani Rad2, Maryam Kiani Borazjani1 1Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran; 2Department of Chemistry, Faculty of Basic Sciences, Shiraz University of Technology, Shiraz, Iran Abstract: The grafting of drugs to the single-walled carbon nanotube (SWCNT) was attained by the initial conversion of carboxylic groups in SWCNT to corresponding acyl chlorides. The active acyl chlorides in SWCNT were subsequently mixed with chemotherapeutic agents having NH, NH2, and OH functional groups to afford the formation of relevant amide and ester, respectively. The covalently grafted drugs to SWCNT were identified by infrared and UV–visible spectroscopy and transmission electron microscopy methods. From a clinical aspect, the grafting of drugs to the SWCNT can be used as a new tool and useful method for potential drug delivery in patients.
Organic functionalization of single-walled carbon nanotubes (SWCNTs) with some chemotherapeutic agents as a potential method for drug delivery  [cached]
Ardeshir Khazaei,Mohammad Navid Soltani Rad,Maryam Kiani Borazjani
International Journal of Nanomedicine , 2010,
Abstract: Ardeshir Khazaei1, Mohammad Navid Soltani Rad2, Maryam Kiani Borazjani11Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran; 2Department of Chemistry, Faculty of Basic Sciences, Shiraz University of Technology, Shiraz, IranAbstract: The grafting of drugs to the single-walled carbon nanotube (SWCNT) was attained by the initial conversion of carboxylic groups in SWCNT to corresponding acyl chlorides. The active acyl chlorides in SWCNT were subsequently mixed with chemotherapeutic agents having NH, NH2, and OH functional groups to afford the formation of relevant amide and ester, respectively. The covalently grafted drugs to SWCNT were identified by infrared and UV–visible spectroscopy and transmission electron microscopy methods. From a clinical aspect, the grafting of drugs to the SWCNT can be used as a new tool and useful method for potential drug delivery in patients.Keywords: grafting of drugs, solubilization
Synergistic enhancement of cancer therapy using a combination of docetaxel and photothermal ablation induced by single-walled carbon nanotubes  [cached]
Wang L,Zhang MY,Zhang N,Shi JJ
International Journal of Nanomedicine , 2011,
Abstract: Lei Wang1, Mingyue Zhang1, Nan Zhang1, Jinjin Shi1, Hongling Zhang1, Min Li1, Chao Lu2, Zhenzhong Zhang1 1School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 2University of Maryland, College Park, MD, USA Background: Single-walled carbon nanotubes (SWNT) are poorly soluble in water, so their applications are limited. Therefore, aqueous solutions of SWNT, designed by noncovalent functionalization and without toxicity, are required for biomedical applications. Methods: In this study, we conjugated docetaxel with SWNT via p-p accumulation and used a surfactant to functionalize SWNT noncovalently. The SWNT were then conjugated with docetaxel (DTX-SWNT) and linked with NGR (Asn-Gly-Arg) peptide, which targets tumor angiogenesis, to obtain a water-soluble and tumor-targeting SWNT-NGR-DTX drug delivery system. Results: SWNT-NGR-DTX showed higher efficacy than docetaxel in suppressing tumor growth in a cultured PC3 cell line in vitro and in a murine S180 cancer model. Tumor volumes in the S180 mouse model decreased considerably under near-infrared radiation compared with the control group. Conclusion: The SWNT-NGR-DTX drug delivery system may be promising for high treatment efficacy with minimal side effects in future cancer therapy. Keywords: single-walled carbon nanotubes, docetaxel, NGR peptide, tumor-targeting, near-infrared radiation
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