News Column

Patent Issued for Drug Delivery by Carbon Nanotube Arrays

August 6, 2014



By a News Reporter-Staff News Editor at Biotech Week -- A patent by the inventors Gharib, Morteza (Altadena, CA); Aria, Adrianus Indrat (Pasadena, CA); Beizai, Masoud (Laguna Hills, CA), filed on September 1, 2011, was published online on July 22, 2014, according to news reporting originating from Alexandria, Virginia, by NewsRx correspondents (see also California Institute of Technology).

Patent number 8784373 is assigned to California Institute of Technology (Pasadena, CA).

The following quote was obtained by the news editors from the background information supplied by the inventors: "Targeted, localized and controlled drug delivery remains a major challenge. In many cases, efficacy of a drug can be improved and the risks of side effects reduced if the therapy is administered locally and/or continuously, rather than through conventional oral ingestion or injection, which produce burst releases. In some cases, dose-limiting toxicity levels are caused by agent losses in vascular travel during transplant procedures. Continuous and accurate local dosing is highly desirable, but remains a major challenge, particularly in the cardiovascular field where requirements for a material's biocompatibility and dosing control are stringent.

"Current diffusion-based drug-delivery platforms suffer from very slow mass-transfer process. The published reports indicate involvement of solid/solid diffusion as well as channel (e.g., tubule) and solvent-help (e.g., capillary, osmotic) mechanisms but not convection. (Tepe, et al. 2007 Touch Briefings 2007--Interventional Cardiology, pp. 61-63; Scheller, et al. 2004 Circulation 110:810-814; Diaz, et al. 2005 J Biol Chem 280:3928-3937; Creel, et al. 2000 Circ Res 86:879-884; Lovich, et al. 2001 J Pharm Sci 90:1324-1335; Zilberman, et al. 2008 J Biomed Mater Res 84A:313-323; Davies 1997 N Engl J Med 336:1312-1314; Arakawa, et al. 2002 Arterioscler Thromb Vasc Biol 22:1002-1007; Parekh, et al. 1997 Gen Pharmac 29:167-172; Hearn, et al. 2009 Nature 458:367-371; Celermajer 2002 European Heart Journal Supplement F:F24-F28; Andersen, et al. 2006 BMC Clinical Pharmacology, published online 13 Jan. 2006; Oreopoulos, et al. 2009 J Structural Biology 168:21-36; Panchagnula, et al. 2004 J Pharm Sci 93:2177-2183; Migliavacca, et al. 2007 Comput Methods Biomech Biomed Engin 10:63-73; Arifin, et al. 2009 Pharmaceutical Research, published online 29 Jul. 2009.) In percutaneous transluminal angioplasty (PCTA) devices, for example, drug washout and overdose remain serious challenges. For oncology applications, for example, localized delivery of sufficient dose of anti-cancer drug via targeted delivery is highly desirable.

"In recent years, carbon nanotubes have attracted attention due to their chemical, mechanical and geometric properties. Carbon nanotubes (CNTs) are allotropes of carbon with a cylindrical nanostructure and are members of the fullerene structural family. Nanotubes are categorized as single-walled nanotubes and multi-walled nanotubes. Carbon nanotubes are strong and stiff materials in terms of tensile strength and elastic modulus respectively. Various techniques have been developed to make nanotubes, such as arc discharge, laser ablation, high-pressure carbon monoxide, and chemical vapor deposition.

"Researches have been reported on CNT-based drug delivery. For example, a recent study was reported on drug delivery using PEGylated-CNTs. (Liu, et al. 2008 Cancer Res. 68: (16), 6652). The reported system is based on covalently attaching drug molecules to PEGylated CNTs. Another research group used carbon nanotube-based tumor-targeted drug delivery system, which consisted of a functionalized CNTs linked to tumor-targeting modules as well as prodrug modules. (Chen, et al. 2008 J Am Chem Soc 130:16778-16785.) In both of the afore-mentioned approaches, functionalization of the CNTs is required, which presents a number of complications and procedural drawbacks.

"One reported example of angioplasty drug delivery is a PTCA balloon coated with paclitaxel in an iopromide matrix. The balloon is inflated for 30-second contact with vascular wall to allow the matrix to dissolve and paclitaxel to migrate into the smooth muscle cell. (Scheller, et al. 2004 Circulation 110:810-814.) Major problems with this device include iopromide being hydrophilic and an X-ray contrast agent. The first causes some drug loss to blood stream (although claimed to be about 6%) and the second leads to adverse reactions for some patients. Furthermore, the balloon still contains about 10% paclitaxel after detachment and only about 15% remains in the plaque.

"Another reported example of angioplasty drug delivery is a system using vascular stents made of paclitaxel-eluting composite fibers to deliver about 40% of drug, most of it over 30 days. (Zilberman, et al. 2008 J Biomed Mater Res 84A:313-323.) Since the main mass-transfer mechanism of this device is diffusion, the rate is inherently slow. These drawbacks are in addition to the well-documented risks and side effects associated with stents.

"For angioplasty drug delivery monitoring, existing technologies typically use a fluorescent dye administered intravenously through a central venous line with a dose adapted to body weight. (Detter, et al. 2007 Circulation 116:1007-1014; Hattori, et al. 2009 Circ Cardiovasc Imaging 2:277-278; Hosono, et al. 2010 Interact CardioVasc Thorac Surg 10:476-477; Tanaka, et al. 2009 J Thorac Cardiovasc Surg 138:133-140; Waseda, et al. 2009 JACC Cardiovascular Imaging 2:604-612.) The illumination is provided by near-infrared laser diodes with a typical output of 80 mW in a field of view of 10 cm in diameter, eliminating tissue warming and eye protection concerns. The fluorescence emission of the excited dye is typically detected by an IR-CCD camera and digitized with a frame grabber that provides real-time recording.

"Therefore, there remains an urgent and unmet need for improved drug delivery systems addressing the above-mentioned shortcomings, particularly in the field of angioplasty drug delivery."

In addition to the background information obtained for this patent, NewsRx journalists also obtained the inventors' summary information for this patent: "The invention is based, in part, on the unique approach to drug delivery using anchored carbon nanotube arrays. In particular, the invention provides targeted, localized, and controlled drug delivery using novel anchored carbon nanotube arrays that carry (e.g., non-covalently) the agent to be delivered, including therapeutic and diagnostic agents.

"In one aspect, the invention generally relates a method for delivering an agent to a patient in situ. The method includes: (a) providing a plurality of carbon nanotubes; (b) depositing the agent to the plurality of carbon nanotubes such that the agent is non-covalently associated with the plurality of carbon nanotubes; placing the plurality of carbon nanotubes deposited with the agent at a target location in the patient's body; and (d) allowing the agent to diffuse from the plurality of carbon nanotubes, thereby delivering the agent in situ.

"In another aspect, the invention generally relates to an implantable drug delivery device. The implantable drug delivery device includes: (a) an implantable device; (b) an array of carbon nanotubes anchored on the implantable drug delivery device; and an agent deposited on the array of carbon nanotubes, wherein the agent is not covalently bound to the carbon nanotubes.

"In yet another aspect, the invention generally relates to a method for monitoring in situ delivery of an agent. The method includes: (a) providing a plurality of carbon nanotubes non-covalently associated thereon a pharmaceutical agent and a second agent capable of exhibiting a spatially detectable signal; (b) placing the plurality of carbon nanotubes at a target location in the patient's body; and measuring the detectable signal exhibited from the second agent to monitor the deliver of the pharmaceutical agent in situ.

"The invention disclosed herein enables improved devices, methods and compositions for treating a number of conditions where targeted, localized, and controlled drug delivery are required."

URL and more information on this patent, see: Gharib, Morteza; Aria, Adrianus Indrat; Beizai, Masoud. Drug Delivery by Carbon Nanotube Arrays. U.S. Patent Number 8784373, filed September 1, 2011, and published online on July 22, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8784373.PN.&OS=PN/8784373RS=PN/8784373

Keywords for this news article include: Surgery, Taxoids, Therapy, Terpenes, Cardiology, Fullerenes, Paclitaxel, Angioplasty, Hydrocarbons, Cardio Device, Cardiovascular, Cycloparaffins, Catheterization, Medical Devices, Carbon Nanotubes, Organic Chemicals, Drug Delivery Systems, Vascular Surgical Procedures, California Institute of Technology.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Biotech Week


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