Most of the existing anticancer drugs are very potent small molecules; their efficacy is constrained by their systemic toxicity, narrow therapeutic window, low drug loading, size control, scale up, cost of formulation but also as a result of drug resistance and limited cellular entry. In the last few years, carbon nanotubes have been projected as a promising carrier for many drugs including anticancer agents because of the high surface area and efficient targeting capabilities. The present work is an attempt to investigate the potentialities of multi-walled carbon nanotubes (MWCNT) as a carrier for targeting 6 Mercaptopurine to cancer tissues. MWCNTs were carboxy functionalized and then loaded with 6 Mercaptopurine (6MP) using the fusion method to produce 6MP loaded CNTs. The conjugate was characterized for drug loading efficiency, in vitro drug release and release kinetics. The result indicated that a maximum of about 65% entrapment was achieved. The loaded nanotubes were shown to release the drug for more than 20 hours and thus controlling the release. The release was found to follow the Zero Order and Hixson Crowell release pattern. Our work established a novel, easy to prepare formulation of MWCNTs with better drug loading efficiency and increased dispersibility of CNTs and thus bioavailability at cancer site with reduced systemic toxicity.
Keywords: Multiwalled Carbon Nanotubes, 6-Mercaptopurine, Anticancer, Fusion Method.
Cancer is amongst the top three killers in modern society, next to heart and cerebrovascular diseases. Treating cancer has always been a challenge because cancer chemotherapeutic agents are cytotoxic and cannot differentiate cancer cells from normal cells. This leads to the destruction or impairment of vi...
... middle of paper ...
...ents like PEG to achieve long blood circulation half-life helping to impede in-vivo opsonization and reduced reticulo-endothelial system uptake[12]. In addition, many oxygen containing groups, mainly carboxyl and hydroxyl, have been found to decorate the surface of CNTs oxidized with strong acids[13].
Several targeted anticancer delivery systems containing 6-Mercaptopurine (6MP) have been reported[14-18]. In the present study, 6MP (6, 7-dihydro-3H-purine-6-thione) (Fig 1) loaded CNTs were developed by slight modification in fusion method[19]. Non-covalent functionalization of Multi walled Carbon Nanotubes (MWCNTs) was achieved using basic treatment followed by treatment with HCl. Functionalized MWCNT were attached with 6MP by sonication in a suitable media (pH 7.4). The formulations were characterized for drug entrapment, in vitro drug release and release kinetics.
The concept of tumor heterogeneity being related to the course of the disease and clinical outcome in cancer patients draws additional attention in the era of personalized medicine (1). Current cancer treatment strategies are based on the site of origin of the primary tumor. However, it was shown that tumors developed from distinct cell types differ in their prognosis and response to cytotoxic therapies (2...
Thermal methods of analysis have been in use for quite a long time. Their application in the analysis of pharmaceutical materials has made it possible for pharmacists and researchers to understand their contents and characteristics. However, thermal methods have several disadvantages that have led researchers to opt for nano-thermal methods of analysis. Nano-thermal analysis methods use special resolution imaging potential that is enhanced by the availability of atomic force microscopy and thermal analysis methods.
The gaseous free radical nitric oxide is an abundant intracellular messenger molecule that plays a central role in maintenance of health, and is heavily involved in signal transduction in various cells of the body [1]. This molecule acts as a mediator in the regulation of cardiac function as well as having an important role in regulating contractility of the heart and maintenance of vascular tone in the cardiovascular system. As one of the most significant individuals in our discovery of nitric oxide, Dr. Robert Furchgott pioneered our understanding of this molecule through his experiments on the vasorelaxant properties of acetylcholine and the subsequent proposal of the presence of the endothelium derived relaxing factor, which was later identified to be nitric oxide [7]. Given the observation that cardiovascular disorders are the number one cause of death in many nations around the world, research into the vasorelaxant properties seems particularly relevant in order to help combat rising rates of vascular hypertension and high blood pressure. In this paper, the properties of nitric oxide are discussed largely with respect to the cardiovascular system. This paper focuses on the synthesis and characteristics of nitric oxide, the mechanisms of action by which nitric oxide works and the regulation of nitric oxide in the body, and finally a short summary of Robert Furchgott’s contributions to the discovery of nitric oxide and its properties.
Hegab Z, Gibbons S, Mamas M, et al. Role of advanced glycation end products in cardiovascular disease. World J Cardiol. 2012 Apr; 4 (4): 20-102.
U.S. Congress, Office of Technology Assessment. 1990. Unconventional Cancer Treatments, OTA-H-405. Washington, D.C.: U.S. Government Printing Office.
Its ability to inhibit sodium channels within brain cells thereby protecting the cells from hypoxia (lack of oxygen)
The well-known “penicillin of cancer drugs” is probably an appropriate nickname of cisplatin due to its world widely use as the first and one of the most effective treatment for numerous cancer diagnoses. One important thing that must be point out is that cisplatin is a very simple inorganic molecule comparing to other cancer drugs which generally are complex organic molecules. In order to design and develop new related cancer drugs, cisplatin has been used as a gold model by many scientists.
In this case study, our concern goes for the chitosan nanoparticles; firstly nanoparticles are able to adsorb and/or encapsulate a drug, thus protecting it against chemical and enzymatic degradation. Furthermore the encapsulated drug may be prevented from crystallization, thus forming a solid solution. Depending on drug solubility in the carrier, a drug load varying from only a few percent up to 50%] Secondly, chitosan is ...
Chemotherapy is the treatment of a tumor with chemical agents to reduce mass or eradicate a tumor completely. There are certain mechanisms by which chemotherapy inhibits cancer. The first mechanism is cell death by cytotoxicity. Some chemical agents in certain amounts are toxic to cells. The cells die due to the toxic...
Why do consumers purchase specific drugs for various ailments, sicknesses or diseases they might have? Why do physicians prescribe certain drugs over competitive drugs that may be available to the public? Why is it that most of us can easily name specific drugs that fit the many ailments of today’s society? On the surface the answer might be as simple as good TV advertising or radio commercials or even internet adds. The truth of matter is the major pharmaceutical manufacturers own the patents on these drugs and this gives them all of the marketing budget and muscle they need to promote the drug and control the pricing. The incentives for larger pharmaceutical companies are very enticing and as a result, they don’t mind spending the time in clinical trials and patent courts to get their drugs approved. Some will even get patents on the process by which the drug is manufactured, ensuring that no competitor can steal the drug or the process. This protects their large financial investment and nearly guarantees a large return for their investors. Many consumer rights groups claim this is nothing more than legalizing monopolies for the biggest manufacturers.
Melanoma is a very metastatic form of cancer that can go from stage 1 at diagnosis to an almost untreatable stage 4 in as little as a month. Furthermore, chemotherap...
... of the need of duplicate revascularization over balloon angioplasty [75]. Both pre- and post -conditioning appears to protect cardiomyocytes at the time of reperfusion therapy. Ischemic post-conditioning is a chain of repetitive intermissions of coronary blood flow administered after a period of ischemia. Inhibition of ONOO−-induced nitro-oxidative stress might pay a critical role in postcon-mediated cardioprotection [76]. Iliodromitis et al also reported that postcon-mediated cardioprotection was in cohorts with reduced nitro-oxidative stress in vivo. The acknowledgment that iNOS activation in cardiac myocytes could be advantageous and that nitriate/NO could have both beneficial and detrimental effects, lead to the dose of 1400W iNOS inhibitor being chosen to significantly inhibit, but not restrict, increase in the level of myocardial iNOS activity after MI [77]
Dialysis tubing is made from regenerated cellulose or cellophane, and is used in clinical circumstances to ensure that molecule have a filtered flow, and that larger solute molecules do not enter the dialysis tubing (Alberts, 2002). Like a cell membrane, dialysis tubing has a semi-permeable membrane, which allows small molecule to permeate through the membrane. Thus, the dialysis tubing mimics the diffusion and osmosis processes of the cell membrane (Alberts, 2002). Although the dialysis tubing has a semi-permeable membrane, which mimics a cell, its structure is different. The me...
The most common type of radiation therapy that is used involves exposure of patients to external radiations. In this method, a beam containing high-energy X-rays is directed to a specific region of the body to irradiate the main tumors. However, the problem with this technique is that the ability to hit normal tissues of adjacent organs (Noda et al., 2009). Different from this, targeted radionuclide therapy functions like chemotherapy. A radionuclide labeled molecule is administered either orally or intravenously such that it delivers radiations that are sufficiently toxic to the site of the disease to kill the target cells (Bolus & Brady, 2011). However, the main difference with chemotherapy is that the drugs or toxins only...
Carbon Carbon is one of the basic elements of matter (Bush 1230-1231). The name carbon comes from the Latin word "carbo" meaning charcoal. Carbon is the sixth most abundant element (Gangson). More than 1,000,000 compounds are made from carbon (Carbon (C)). "The Element Carbon is defined as a naturally abundant non-metallic element that occurs in many inorganic and in all organic compounds, exists freely as graphite and diamond and as a constituent of coal, limestone, and petroleum, and is capable of chemical self-bonding to form an enormous number of chemically, biologically, and commercially important molecules.